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InvivoGen tlr8 agonist

(A-C) Trophoblast cells were transfected with a scramble control (control), a Let-7b-5p mimic or a Let-7b-5p inhibitor. (A) After 24 hrs and 72 hrs, Let-7b-5p expression was measured by RT-qPCR and expressed as fold change (FC) relative to the control (n=6-9; * p <0.05). (C) After 48 hrs trophoblast cell viability was measured (n=4). (C) After 48 hrs trophoblast cell migration was measured (n=6-8; * p <0.05). (D-E) Trophoblast cells were treated: (D) for 24 hrs with no treatment (NT), the TLR7 inhibitor, IRS661, or the <t>TLR8</t> inhibitor, CUCPT9a (n=9; * p <0.05), or (E) for 48hrs with NT, the TLR7 agonist, R837, or the TLR8 agonist TL8-506 (n=14; * p <0.05), after which cell migration was measured. (F) Trophoblast cells were transfected with a scramble control or a Let-7b-5p mimic and then treated with either media, IRS661 or CUCPT9a. After 24 hrs, cell migration was measured and data are shown as the fold change (FC) of trophoblast migration under Let-7b-5p mimic conditions relative to the scramble control (n=6; * p <0.05). (G) Trophoblast cells were treated with NT, IRS661 or CUCPT9a and after 24 hrs, cell viability was measured (n=3).

Tlr8 Agonist, supplied by InvivoGen, used in various techniques. Bioz Stars score: 96/100, based on 73 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
https://www.bioz.com/product/tlr8+tl8+506/TL8-506/bio_rxiv__64898__2026__08__03__742516-41-34-39
Average 96 stars, based on 73 article reviews

tlr8 agonist - by Bioz Stars, 2026-10

96/100 stars

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1) Product Images from "Let-7b-5p differentially regulates human first trimester trophoblast migration and sFlt-1 through TLR7 and TLR8"

Article Title: Let-7b-5p differentially regulates human first trimester trophoblast migration and sFlt-1 through TLR7 and TLR8

Journal: bioRxiv

doi: 10.64898/2026.08.03.742516

Figure Legend Snippet: (A-C) Trophoblast cells were transfected with a scramble control (control), a Let-7b-5p mimic or a Let-7b-5p inhibitor. (A) After 24 hrs and 72 hrs, Let-7b-5p expression was measured by RT-qPCR and expressed as fold change (FC) relative to the control (n=6-9; * p <0.05). (C) After 48 hrs trophoblast cell viability was measured (n=4). (C) After 48 hrs trophoblast cell migration was measured (n=6-8; * p <0.05). (D-E) Trophoblast cells were treated: (D) for 24 hrs with no treatment (NT), the TLR7 inhibitor, IRS661, or the TLR8 inhibitor, CUCPT9a (n=9; * p <0.05), or (E) for 48hrs with NT, the TLR7 agonist, R837, or the TLR8 agonist TL8-506 (n=14; * p <0.05), after which cell migration was measured. (F) Trophoblast cells were transfected with a scramble control or a Let-7b-5p mimic and then treated with either media, IRS661 or CUCPT9a. After 24 hrs, cell migration was measured and data are shown as the fold change (FC) of trophoblast migration under Let-7b-5p mimic conditions relative to the scramble control (n=6; * p <0.05). (G) Trophoblast cells were treated with NT, IRS661 or CUCPT9a and after 24 hrs, cell viability was measured (n=3).

Techniques Used: Transfection, Control, Expressing, Quantitative RT-PCR, Migration

Modification:

Article Title: Small molecule compound inhibiting signal transmission path of TLR7 and TLR9 and use thereof
Article Snippet: The cells were cultured in RPMI 1640 (HyClone Laboratories, Inc.) and t differentiated into macrophages by applying 80 nM phorbol 12-myristate 13-acetate (PMA; Sigma-Aldrich Co., St. Louis, MO, USA) for 48 h. All cell lines were maintained in a humidified incubator (37° C., 5% CO2), and the medium was replaced after overnight incubation. .. Agonists specific to TLR1/TLR2 (Pam3CSK4), TLR2/TLR6 (FSL-1), TLR3 (Poly I:C), TLR7 (imiquimod), and TLR8 (TL8-506) were purchased from InvivoGen Ltd. (Hong-Kong, China), and a TLR4-specific agonist (LPS from E. coli O111:B4) was purchased from Sigma-Aldrich, Inc. For TLR9-specific stimulation, class C CpG-ODN (ODN2395, 5′-TCG TCG TTT TCG GCG CGC GCC G-3′) having full phosphorothioate backbone modification was synthesized (Bioneer, Inc., Daejeon, Korea). ..

Synthesized:

other:

Article Title: Discovery of Novel Small Molecule Dual Inhibitor Targeting Toll-Like Receptors 7 and 9.
Article Snippet: The aberrant secretion of proinflammatory cytokines by immune cells is the principal cause of inflammatory diseases, such as systemic lupus erythematosus and rheumatoid arthritis.. Toll-like receptor 7 (TLR7) and TLR9, sequestered to the endosomal compartment of dendritic cells and macrophages, are closely associated with the initiation and progression of these diseases.. Therefore, the development of drugs targeting dysregulated endosomal TLRs is imperative to mitigate systemic inflammation.

Image Search Results

Journal: bioRxiv

Article Title: Let-7b-5p differentially regulates human first trimester trophoblast migration and sFlt-1 through TLR7 and TLR8

doi: 10.64898/2026.08.03.742516

Figure Lengend Snippet: (A-C) Trophoblast cells were transfected with a scramble control (control), a Let-7b-5p mimic or a Let-7b-5p inhibitor. (A) After 24 hrs and 72 hrs, Let-7b-5p expression was measured by RT-qPCR and expressed as fold change (FC) relative to the control (n=6-9; * p <0.05). (C) After 48 hrs trophoblast cell viability was measured (n=4). (C) After 48 hrs trophoblast cell migration was measured (n=6-8; * p <0.05). (D-E) Trophoblast cells were treated: (D) for 24 hrs with no treatment (NT), the TLR7 inhibitor, IRS661, or the TLR8 inhibitor, CUCPT9a (n=9; * p <0.05), or (E) for 48hrs with NT, the TLR7 agonist, R837, or the TLR8 agonist TL8-506 (n=14; * p <0.05), after which cell migration was measured. (F) Trophoblast cells were transfected with a scramble control or a Let-7b-5p mimic and then treated with either media, IRS661 or CUCPT9a. After 24 hrs, cell migration was measured and data are shown as the fold change (FC) of trophoblast migration under Let-7b-5p mimic conditions relative to the scramble control (n=6; * p <0.05). (G) Trophoblast cells were treated with NT, IRS661 or CUCPT9a and after 24 hrs, cell viability was measured (n=3).

Article Snippet: In other experiments, trophoblast cells, in the absence of any transfection, were treated with either no treatment (NT), IRS661 at 5μM, CUCPT9a at 2.5 μM, the TLR7 agonist, R837 at 5μg/ml (Invivogen), or the TLR8 agonist, TL8-506 at 5μg/ml (Invivogen).

Techniques: Transfection, Control, Expressing, Quantitative RT-PCR, Migration

( A ) The family tree depicts individuals with the TLR8 variant. Solid black boxes represent males P1 and P2 with the germline variant, while half-black circles indicate heterozygous female carriers. ND, not determined. ( B ) Sanger sequencing of the family members’ DNA confirms the presence of the TLR8 variant. ( C ) Leucine-rich repeat (LRR) TLR8 with the Z-loop (PDB ID: 3W3G). The A518 variant in LRR 16 is highlighted in purple. Previously reported variants from Aluri et al. , Fejtkova et al. , and Liang et al. are denoted in cyan.

Journal: JCI Insight

Article Title: Structural modeling and functional characterization of a novel gain-of-function TLR8 variant causing severe inflammatory syndrome

doi: 10.1172/jci.insight.187422

Figure Lengend Snippet: ( A ) The family tree depicts individuals with the TLR8 variant. Solid black boxes represent males P1 and P2 with the germline variant, while half-black circles indicate heterozygous female carriers. ND, not determined. ( B ) Sanger sequencing of the family members’ DNA confirms the presence of the TLR8 variant. ( C ) Leucine-rich repeat (LRR) TLR8 with the Z-loop (PDB ID: 3W3G). The A518 variant in LRR 16 is highlighted in purple. Previously reported variants from Aluri et al. , Fejtkova et al. , and Liang et al. are denoted in cyan.

Article Snippet: Cells were then stimulated with either TLR8 agonists — 50 ng/mL, 100 ng/mL, or 1 μg/mL TL8-506 (tlrl-tl8506, InvivoGen) and 1 μg/mL ORN 06 (tlrl-orn6, InvivoGen) — or 1 μg/mL CL097 TLR7 agonist.

Techniques: Variant Assay, Sequencing

( A ) Ribbon diagram of the side view of TLR8 receptor homodimer (PDB ID: 4R08) with the 2 chains colored gray and pink, and residue 518 indicated in a purple halo, positioned at the interface of the homodimer and the uridine residue in ball-and-stick representation in orange with an orange halo. ( B ) Comparison of hydrogen bonds in the WT protein (left) and A518T variant (right). The hydrogen bonds that are conserved in both proteins are shown as red dashed lines, and the additional hydrogen bonds formed by the A518T variant are shown as black dashed lines and a blue halo. A gray rectangle highlights the differences in hydrogen bonding patterns in the WT and A518T variant proteins. The uridine residue (URI) is represented with ball and stick in orange with an orange halo around it, and the atoms are colored according to the elements with red and blue spheres representing oxygen and nitrogen, respectively. The hydrogen-bonded residues are numbered and shown with ball-and-stick representation with their respective 3-letter codes. ( C ) Comparison of the Δ vibrational entropy energy of A518T variant with respect to the WT protein in the ligand-bound activated state (green) and the unbound inactivated state (blue) with the residue numbers on the x axis, calculated by DynaMut. ( D ) Comparison of water-mediated interchain hydrogen bonds in the WT protein in the activated state (dark gray), WT protein in the inactivated state (light gray), A518T variant in the activated state (blue), and A518T variant in the inactivated state (green), based on molecular dynamics simulations with OpenMM.

Journal: JCI Insight

Article Title: Structural modeling and functional characterization of a novel gain-of-function TLR8 variant causing severe inflammatory syndrome

doi: 10.1172/jci.insight.187422

Figure Lengend Snippet: ( A ) Ribbon diagram of the side view of TLR8 receptor homodimer (PDB ID: 4R08) with the 2 chains colored gray and pink, and residue 518 indicated in a purple halo, positioned at the interface of the homodimer and the uridine residue in ball-and-stick representation in orange with an orange halo. ( B ) Comparison of hydrogen bonds in the WT protein (left) and A518T variant (right). The hydrogen bonds that are conserved in both proteins are shown as red dashed lines, and the additional hydrogen bonds formed by the A518T variant are shown as black dashed lines and a blue halo. A gray rectangle highlights the differences in hydrogen bonding patterns in the WT and A518T variant proteins. The uridine residue (URI) is represented with ball and stick in orange with an orange halo around it, and the atoms are colored according to the elements with red and blue spheres representing oxygen and nitrogen, respectively. The hydrogen-bonded residues are numbered and shown with ball-and-stick representation with their respective 3-letter codes. ( C ) Comparison of the Δ vibrational entropy energy of A518T variant with respect to the WT protein in the ligand-bound activated state (green) and the unbound inactivated state (blue) with the residue numbers on the x axis, calculated by DynaMut. ( D ) Comparison of water-mediated interchain hydrogen bonds in the WT protein in the activated state (dark gray), WT protein in the inactivated state (light gray), A518T variant in the activated state (blue), and A518T variant in the inactivated state (green), based on molecular dynamics simulations with OpenMM.

Techniques: Residue, Comparison, Variant Assay

( A ) Histogram plots of p–NF-κB of CD45 + CD14 + monocytes from freshly isolated PBMCs in family members relative to healthy males (CTRm; n = 3) (left) with the corresponding MFI (right). Data represent mean ± SEM for healthy male controls. ( B ) Histogram plots of TLR8 of CD45 + CD14 + monocytes from freshly isolated PBMCs in family members relative to healthy males (CTRm; n = 3) (left) and the ratio of ∆ p–NF-κB + to TLR8 + of CD45 + CD14 + monocytes (right). Data represent mean ± SEM for healthy male controls. ( C ) Volcano plot illustrating differentially expressed genes in unstimulated CD14 + CD16 – monocytes isolated from healthy male controls ( n = 4) compared with family members (P1 and P2). Genes with significant upregulation and downregulation are highlighted based on adjusted P values and fold change thresholds. ( D ) Bubble plot representing the top enriched pathways identified from the differentially expressed genes. Bubble size corresponds to the percentage of genes involved, and color intensity reflects the significance of pathway enrichment.

Journal: JCI Insight

Article Title: Structural modeling and functional characterization of a novel gain-of-function TLR8 variant causing severe inflammatory syndrome

doi: 10.1172/jci.insight.187422

Figure Lengend Snippet: ( A ) Histogram plots of p–NF-κB of CD45 + CD14 + monocytes from freshly isolated PBMCs in family members relative to healthy males (CTRm; n = 3) (left) with the corresponding MFI (right). Data represent mean ± SEM for healthy male controls. ( B ) Histogram plots of TLR8 of CD45 + CD14 + monocytes from freshly isolated PBMCs in family members relative to healthy males (CTRm; n = 3) (left) and the ratio of ∆ p–NF-κB + to TLR8 + of CD45 + CD14 + monocytes (right). Data represent mean ± SEM for healthy male controls. ( C ) Volcano plot illustrating differentially expressed genes in unstimulated CD14 + CD16 – monocytes isolated from healthy male controls ( n = 4) compared with family members (P1 and P2). Genes with significant upregulation and downregulation are highlighted based on adjusted P values and fold change thresholds. ( D ) Bubble plot representing the top enriched pathways identified from the differentially expressed genes. Bubble size corresponds to the percentage of genes involved, and color intensity reflects the significance of pathway enrichment.

Techniques: Isolation

( A ) Western blot against TLR8, p–NF-κB, total NF-κB, and γ-tubulin (γ-TUB) in BlaER1 TLR8 –/– cells with the insertion of the TLR8 WT protein or the p.A518T and the previously published p.D543A (loss-of-function) TLR8 variants. Cells were stimulated with 100 ng/mL TL8-506 agonist for 15 minutes (left), and the ratio of p–NF-κB to total NF-κB to TLR8 levels, normalized to TLR8 levels, is shown (right). Statistical significance between groups was assessed using a 2-way ANOVA multiple-comparison test. Data represent mean ± SEM of n = 4 experiments. RQ, relative quantification. ( B ) IL-6 quantification of BlaER1 TLR8 –/– cells with the insertion of the TLR8 WT protein or the p.A518T and p.D543A (loss-of-function) variants. Cells were stimulated with 1 μg/mL TL8-506 and 1 μg/mL ORN 06 agonists. Data are presented after the subtraction of the unstimulated measurements. Statistical significance between groups was assessed using a 2-way ANOVA multiple-comparison test. Data represent mean ± SEM of n = 3–4 experiments. Differences between groups were considered significant at P values less than 0.05.

Journal: JCI Insight

Article Title: Structural modeling and functional characterization of a novel gain-of-function TLR8 variant causing severe inflammatory syndrome

doi: 10.1172/jci.insight.187422

Figure Lengend Snippet: ( A ) Western blot against TLR8, p–NF-κB, total NF-κB, and γ-tubulin (γ-TUB) in BlaER1 TLR8 –/– cells with the insertion of the TLR8 WT protein or the p.A518T and the previously published p.D543A (loss-of-function) TLR8 variants. Cells were stimulated with 100 ng/mL TL8-506 agonist for 15 minutes (left), and the ratio of p–NF-κB to total NF-κB to TLR8 levels, normalized to TLR8 levels, is shown (right). Statistical significance between groups was assessed using a 2-way ANOVA multiple-comparison test. Data represent mean ± SEM of n = 4 experiments. RQ, relative quantification. ( B ) IL-6 quantification of BlaER1 TLR8 –/– cells with the insertion of the TLR8 WT protein or the p.A518T and p.D543A (loss-of-function) variants. Cells were stimulated with 1 μg/mL TL8-506 and 1 μg/mL ORN 06 agonists. Data are presented after the subtraction of the unstimulated measurements. Statistical significance between groups was assessed using a 2-way ANOVA multiple-comparison test. Data represent mean ± SEM of n = 3–4 experiments. Differences between groups were considered significant at P values less than 0.05.

Techniques: Western Blot, Comparison, Quantitative Proteomics

( A ) Western blot against TLR8, γ-TUB, and lactate dehydrogenase A (LDHA) of cycloheximide-incubated (CHX-incubated) HEK BN1 cells expressing TLR8 WT or the p.A518T and the previously published p.G572V (gain-of-function) variants (left), and Western blot quantification (right). Statistical significance between groups was assessed using a 2-way ANOVA multiple-comparison test. Data represent mean ± SEM of n = 4 experiments. ( B ) Western blot analysis of HA-tagged immunoprecipitated proteins from HEK293T cell extracts treated with (+) or without (–) the proteasome inhibitor MG132 and CHX. Cells were transfected with HA-tagged constructs and subjected to immunoprecipitation using anti-HA antibody. Left: Blots were probed with antibodies against ubiquitin, TLR8, and the HA tag to assess protein ubiquitination, TLR8 levels, and expression of the HA-tagged construct. Right: Quantification of ubiquitin signal normalized to TLR8 (top) and to HA (bottom) signals, showing the relative levels of TLR8 ubiquitination and overall ubiquitination of HA-tagged proteins. Statistical significance was assessed with a 2-way ANOVA multiple-comparison test. Data represent mean ± SEM of n = 3 experiments. Differences between groups were considered significant at P values less than 0.05.

Journal: JCI Insight

Article Title: Structural modeling and functional characterization of a novel gain-of-function TLR8 variant causing severe inflammatory syndrome

doi: 10.1172/jci.insight.187422

Figure Lengend Snippet: ( A ) Western blot against TLR8, γ-TUB, and lactate dehydrogenase A (LDHA) of cycloheximide-incubated (CHX-incubated) HEK BN1 cells expressing TLR8 WT or the p.A518T and the previously published p.G572V (gain-of-function) variants (left), and Western blot quantification (right). Statistical significance between groups was assessed using a 2-way ANOVA multiple-comparison test. Data represent mean ± SEM of n = 4 experiments. ( B ) Western blot analysis of HA-tagged immunoprecipitated proteins from HEK293T cell extracts treated with (+) or without (–) the proteasome inhibitor MG132 and CHX. Cells were transfected with HA-tagged constructs and subjected to immunoprecipitation using anti-HA antibody. Left: Blots were probed with antibodies against ubiquitin, TLR8, and the HA tag to assess protein ubiquitination, TLR8 levels, and expression of the HA-tagged construct. Right: Quantification of ubiquitin signal normalized to TLR8 (top) and to HA (bottom) signals, showing the relative levels of TLR8 ubiquitination and overall ubiquitination of HA-tagged proteins. Statistical significance was assessed with a 2-way ANOVA multiple-comparison test. Data represent mean ± SEM of n = 3 experiments. Differences between groups were considered significant at P values less than 0.05.

Techniques: Western Blot, Incubation, Expressing, Comparison, Immunoprecipitation, Transfection, Construct, Ubiquitin Proteomics

Dynamics of immune cell subsets in response to agonist stimulation. A Schematic of the experimental workflow. Immune profiling by flow cytometry was performed 48 h after a single intratumoral injection of PRR agonists. B Percentage of CD45 + leukocytes among live cells following intratumoral administration of different agonists: TLR3 agonist poly IC (25 µg/tumor), TLR7 agonist imiquimod hydrochloride (25 µg/tumor), TLR8 agonist TL8-506 (10 µg/tumor), TLR9 agonist CpG ODN 2395 (50 µg/tumor), STING agonist ADU-S100 ammonium salt (25 µg/tumor), NOD1 agonist Tri-DAP (10 µg/tumor), and NOD2 agonist murabutide (5 µg/tumor). C Proportion of cDCs within the CD45 + population. D Percentage of ZsGreen + cells among DCs. E Proportion of macrophages within the CD45 + population. F Percentage of ZsGreen + cells among macrophages. G Proportion of CD8 + T cells within the CD45 + compartment. H Proportion of cCD4 + T cells within the CD45 + compartment. I Proportion of Tregs within the CD45 + compartment, pooled from two independent experiments. J Ratio of cCD4 + T cells to Tregs. (K) Ratio of CD8 + T cells to Tregs. Data represent the mean ± SEM ( n = 8 mice per group). Statistical comparisons were performed using one-way ANOVA. * P < 0.05; ** P < 0.01; *** P < 0.001; **** P < 0.0001

Journal: Cancer Immunology, Immunotherapy : CII

Article Title: TLR8 agonists remodel the tumor immune microenvironment through PF4-dependent T cell recruitment and ancillary mechanisms

doi: 10.1007/s00262-026-04329-8

Figure Lengend Snippet: Dynamics of immune cell subsets in response to agonist stimulation. A Schematic of the experimental workflow. Immune profiling by flow cytometry was performed 48 h after a single intratumoral injection of PRR agonists. B Percentage of CD45 + leukocytes among live cells following intratumoral administration of different agonists: TLR3 agonist poly IC (25 µg/tumor), TLR7 agonist imiquimod hydrochloride (25 µg/tumor), TLR8 agonist TL8-506 (10 µg/tumor), TLR9 agonist CpG ODN 2395 (50 µg/tumor), STING agonist ADU-S100 ammonium salt (25 µg/tumor), NOD1 agonist Tri-DAP (10 µg/tumor), and NOD2 agonist murabutide (5 µg/tumor). C Proportion of cDCs within the CD45 + population. D Percentage of ZsGreen + cells among DCs. E Proportion of macrophages within the CD45 + population. F Percentage of ZsGreen + cells among macrophages. G Proportion of CD8 + T cells within the CD45 + compartment. H Proportion of cCD4 + T cells within the CD45 + compartment. I Proportion of Tregs within the CD45 + compartment, pooled from two independent experiments. J Ratio of cCD4 + T cells to Tregs. (K) Ratio of CD8 + T cells to Tregs. Data represent the mean ± SEM ( n = 8 mice per group). Statistical comparisons were performed using one-way ANOVA. * P < 0.05; ** P < 0.01; *** P < 0.001; **** P < 0.0001

Article Snippet: When tumors reached approximately 200 mm 3 , PRR agonists were administered via intratumoral injection at the following doses: TLR3 agonist poly(I:C) (Sigma-Aldrich, #42,424–50-0; 25 μg/tumor); TLR7 agonist imiquimod hydrochloride (MedChemExpress, #HY-B0180A; 25 μg/tumor); TLR8 agonist TL8-506 (InvivoGen, #tlrl-tl8506; 10 μg/tumor); TLR8 agonist motolimod (MedChemExpress, #HY-13773; 50 μg/tumor); TLR9 agonist CpG ODN 2395 (Class C) (InvivoGen, #tlrl-2395–1; 50 μg/tumor); STING agonist ADU-S100 ammonium salt (MedChemExpress, #HY-12885B; 25 μg/tumor); NOD1 agonist Tri-DAP (InvivoGen, #tlrl-tdap; 10 μg/tumor); and NOD2 agonist murabutide (InvivoGen, #tlrl-mbt; 5 μg/tumor).

Techniques: Flow Cytometry, Injection

Immune modulation and antitumor effects of TLR8 agonists. A Flow cytometric analysis of CD45 + leukocytes was performed 48 h after three intratumoral injections of TL8-506 (10 µg/tumor) or motolimod (50 µg/tumor) ( n = 6). B Percentage of cDCs within the CD45 + population and proportion of ZsGreen + cells among cDCs ( n = 6). C Percentage of macrophages within the CD45 + population and proportion of ZsGreen + cells among macrophages ( n = 6). D Frequency of cCD4 + T cells, CD8 + T cells, and Tregs within the CD45 + compartment ( n = 6). E Ratios of cCD4 + T cells to Tregs and CD8 T cells to Tregs ( n = 6). F , G Tumor growth curves and terminal tumor weights of AKR and MC38 tumors in C57BL/6 mice administered TL8-506 or motolimod every 3 days ( n = 5). H , I Tumor growth curves and terminal tumor weights of AKR and MC38 tumors in nude mice administered motolimod every three days ( n = 5). J , K Macrophage phagocytosis of CFSE-labeled tumor cells following motolimod stimulation ( n = 5). Data represent the mean ± SEM. Data in panels A–G were analyzed using one-way ANOVA, and data in panels H–K were analyzed using Student’s t-tests. * P < 0.05; ** P < 0.01; *** P < 0.001; **** P < 0.0001

Journal: Cancer Immunology, Immunotherapy : CII

Article Title: TLR8 agonists remodel the tumor immune microenvironment through PF4-dependent T cell recruitment and ancillary mechanisms

doi: 10.1007/s00262-026-04329-8

Figure Lengend Snippet: Immune modulation and antitumor effects of TLR8 agonists. A Flow cytometric analysis of CD45 + leukocytes was performed 48 h after three intratumoral injections of TL8-506 (10 µg/tumor) or motolimod (50 µg/tumor) ( n = 6). B Percentage of cDCs within the CD45 + population and proportion of ZsGreen + cells among cDCs ( n = 6). C Percentage of macrophages within the CD45 + population and proportion of ZsGreen + cells among macrophages ( n = 6). D Frequency of cCD4 + T cells, CD8 + T cells, and Tregs within the CD45 + compartment ( n = 6). E Ratios of cCD4 + T cells to Tregs and CD8 T cells to Tregs ( n = 6). F , G Tumor growth curves and terminal tumor weights of AKR and MC38 tumors in C57BL/6 mice administered TL8-506 or motolimod every 3 days ( n = 5). H , I Tumor growth curves and terminal tumor weights of AKR and MC38 tumors in nude mice administered motolimod every three days ( n = 5). J , K Macrophage phagocytosis of CFSE-labeled tumor cells following motolimod stimulation ( n = 5). Data represent the mean ± SEM. Data in panels A–G were analyzed using one-way ANOVA, and data in panels H–K were analyzed using Student’s t-tests. * P < 0.05; ** P < 0.01; *** P < 0.001; **** P < 0.0001

Techniques: Labeling

TLR8 agonist activates PF4-CXCR3 pathway to shape the TIME. A t-SNE plot showing the distribution of all cells from the control and agonist-treated groups combined ( n = 15,745 cells). B t-SNE plot depicting the distribution of distinct immune cell types. C Dot plot displaying the marker genes used to define each immune cell population. D Density plot showing the distribution of Tlr8-expressing cells across the t-SNE map. E Violin plot illustrating Tlr8 expression levels across different immune cell types. F Circle plot depicting the strength of Pf4–Cxcr3 receptor–ligand interactions between distinct cell types in the control and motolimod-treated groups. G Differential gene expression profiles of neutrophils, macrophages, cDC2, and CD8 + T cells. H Bubble plot comparing changes in specific receptor–ligand interactions between the control and motolimod-treated groups, focusing on macrophage-to-cCD4 + T signaling, cDC2-to-cCD4 + T signaling, and CD8 + T-to-cCD4 + T signaling. I Violin plot showing differential expression of Cxcr3 in cCD4 + T and Tregs, analyzed using the Wilcoxon rank-sum test. ns, not significant; ** P < 0.01

Journal: Cancer Immunology, Immunotherapy : CII

Article Title: TLR8 agonists remodel the tumor immune microenvironment through PF4-dependent T cell recruitment and ancillary mechanisms

doi: 10.1007/s00262-026-04329-8

Figure Lengend Snippet: TLR8 agonist activates PF4-CXCR3 pathway to shape the TIME. A t-SNE plot showing the distribution of all cells from the control and agonist-treated groups combined ( n = 15,745 cells). B t-SNE plot depicting the distribution of distinct immune cell types. C Dot plot displaying the marker genes used to define each immune cell population. D Density plot showing the distribution of Tlr8-expressing cells across the t-SNE map. E Violin plot illustrating Tlr8 expression levels across different immune cell types. F Circle plot depicting the strength of Pf4–Cxcr3 receptor–ligand interactions between distinct cell types in the control and motolimod-treated groups. G Differential gene expression profiles of neutrophils, macrophages, cDC2, and CD8 + T cells. H Bubble plot comparing changes in specific receptor–ligand interactions between the control and motolimod-treated groups, focusing on macrophage-to-cCD4 + T signaling, cDC2-to-cCD4 + T signaling, and CD8 + T-to-cCD4 + T signaling. I Violin plot showing differential expression of Cxcr3 in cCD4 + T and Tregs, analyzed using the Wilcoxon rank-sum test. ns, not significant; ** P < 0.01

Techniques: Control, Marker, Expressing, Gene Expression, Quantitative Proteomics

TLR8 agonist induces PF4 expression through NF-κB signaling pathway. A , B qRT-PCR analysis of Pf4 expression in mouse and human macrophages in the motolimod-treated and control groups ( n = 3). C , D Luminescence assay showing NF-κB pathway activation in mouse and human macrophages following motolimod stimulation ( n = 3). E , F qRT-PCR analysis of Rela expression in Rela -knockdown and control mouse and human macrophages with or without motolimod treatment ( n = 3). G , H Western blotting showing p65 protein levels in RELA -knockdown and control mouse and human macrophages with or without motolimod treatment. I , J qRT-PCR analysis of Pf4 / PF4 expression in Rela / RELA -knockdown and control mouse and human macrophages with or without motolimod treatment ( n = 3). K ELISA quantification of Pf4 levels in the culture supernatant from Rela -knockdown and control mouse macrophages with or without motolimod treatment ( n = 3). Data represent the mean ± SEM. Statistical comparisons were performed using Student’s t-tests. * P < 0.05; ** P < 0.01; *** P < 0.001; **** P < 0.0001

Journal: Cancer Immunology, Immunotherapy : CII

Article Title: TLR8 agonists remodel the tumor immune microenvironment through PF4-dependent T cell recruitment and ancillary mechanisms

doi: 10.1007/s00262-026-04329-8

Figure Lengend Snippet: TLR8 agonist induces PF4 expression through NF-κB signaling pathway. A , B qRT-PCR analysis of Pf4 expression in mouse and human macrophages in the motolimod-treated and control groups ( n = 3). C , D Luminescence assay showing NF-κB pathway activation in mouse and human macrophages following motolimod stimulation ( n = 3). E , F qRT-PCR analysis of Rela expression in Rela -knockdown and control mouse and human macrophages with or without motolimod treatment ( n = 3). G , H Western blotting showing p65 protein levels in RELA -knockdown and control mouse and human macrophages with or without motolimod treatment. I , J qRT-PCR analysis of Pf4 / PF4 expression in Rela / RELA -knockdown and control mouse and human macrophages with or without motolimod treatment ( n = 3). K ELISA quantification of Pf4 levels in the culture supernatant from Rela -knockdown and control mouse macrophages with or without motolimod treatment ( n = 3). Data represent the mean ± SEM. Statistical comparisons were performed using Student’s t-tests. * P < 0.05; ** P < 0.01; *** P < 0.001; **** P < 0.0001

Techniques: Expressing, Quantitative RT-PCR, Control, Luminescence Assay, Activation Assay, Knockdown, Western Blot, Enzyme-linked Immunosorbent Assay

TLR8 agonist enhances the efficacy of anti-PD-1 therapy. A Experimental workflow showing treatment schedule for AKR tumor-bearing C57BL/6 mice receiving intratumoral motolimod and intraperitoneal anti-PD-1 (αPD-1) antibody, alone or in combination. B , C Tumor growth curves and survival analysis of AKR tumor-bearing mice treated with the indicated regimens ( n = 7 mice per group). D Experimental workflow showing treatment schedule and details for MC38 tumors in C57BL/6 mice receiving intratumoral motolimod and intraperitoneal αPD-1 antibody, alone or in combination. E , F Tumor growth curves and survival analysis of MC38 tumor-bearing mice treated with the indicated regimens ( n = 7 mice per group). Data represent the mean ± SEM. Tumor growth curves were analyzed using one-way ANOVA, and survival curves were analyzed using log-rank testing. * P < 0.05; ** P < 0.01; *** P < 0.001; **** P < 0.0001

Journal: Cancer Immunology, Immunotherapy : CII

Article Title: TLR8 agonists remodel the tumor immune microenvironment through PF4-dependent T cell recruitment and ancillary mechanisms

doi: 10.1007/s00262-026-04329-8

Figure Lengend Snippet: TLR8 agonist enhances the efficacy of anti-PD-1 therapy. A Experimental workflow showing treatment schedule for AKR tumor-bearing C57BL/6 mice receiving intratumoral motolimod and intraperitoneal anti-PD-1 (αPD-1) antibody, alone or in combination. B , C Tumor growth curves and survival analysis of AKR tumor-bearing mice treated with the indicated regimens ( n = 7 mice per group). D Experimental workflow showing treatment schedule and details for MC38 tumors in C57BL/6 mice receiving intratumoral motolimod and intraperitoneal αPD-1 antibody, alone or in combination. E , F Tumor growth curves and survival analysis of MC38 tumor-bearing mice treated with the indicated regimens ( n = 7 mice per group). Data represent the mean ± SEM. Tumor growth curves were analyzed using one-way ANOVA, and survival curves were analyzed using log-rank testing. * P < 0.05; ** P < 0.01; *** P < 0.001; **** P < 0.0001

Techniques:

a PBMC-derived monocytes were stimulated for 4 h with M. stadtmanae , M. smithii , or the TLR8 agonist TL8-506 (1 μg/mL), with or without pre-treatment using the TLR8 inhibitor CU-CPT9a. Expression levels of representative Class I and Class II genes were measured by RT-qPCR and normalized to the housekeeping gene HPRT . Data are presented as fold induction relative to unstimulated controls. Each data point represents an individual donor ( n = 3); bars indicate mean ± SD. Statistical significance between paired conditions was assessed using a two-tailed paired t -test. b Volcano plots were generated from RNA-seq data of PBMC-derived monocytes using Sleuth. For each condition, log 2 FC (x-axis) was plotted against –log 10 p -value (y-axis). The inhibitor only, M. stadtmanae and M. smithii groups were compared to the unstimulated control, while the M. stadtmanae + inhibitor and M. smithii + inhibitor groups were compared to the inhibitor-only control. Red dots represent upregulated DEGs genes, blue dots represent downregulated DEGs genes, and gray dots denote non-significant changes. The five most upregulated and five most downregulated genes (by log 2 FC) are labeled. Total numbers of DEGs for each comparison are indicated in boxed annotations. c The 3D PCA plot displays the first three principal components (PC1, PC2, and PC3), which capture the major sources of variance in the dataset. Samples are color-coded by experimental condition: unstimulated control, TLR8 inhibitor only, M. smithii (4 h), M. stadtmanae (4 h), M. smithii (4 h) + inhibitor, and M. stadtmanae (4 h) + inhibitor. d A Venn diagram illustrates the overlap of upregulated DEGs in response to 4 h stimulation with M. smithii or M. stadtmanae , with or without TLR8 inhibitor treatment. e A dot plot shows paired log 2 FC of shared upregulated genes. Each dot represents a DEG detected under both M. stadtmanae and M. stadtmanae + TLR8 inhibitor conditions. The x-axis shows the log 2 FC under M. stadtmanae stimulation alone, and the y-axis shows the corresponding log 2 FC under inhibitor treatment. The long dashed diagonal line (y = x) indicates equal expression between conditions. Two additional short dashed lines, drawn parallel to the diagonal at ±1 log 2 FC difference, demarcate three groups: (1) blue dots, downregulated by inhibitor treatment (log 2 FC decrease ≥ 1); (2) gray dots, largely unaffected (difference between –1 and +1); and (3) red dots, increased by inhibitor treatment (log 2 FC increase ≥ 1).

Journal: bioRxiv

Article Title: Differential methanogenic archaea-induced TLR8-dependent signaling is governed by NF-κB p65- and STAT1/2-controlled gene classes

doi: 10.1101/2025.09.30.679018

Figure Lengend Snippet: a PBMC-derived monocytes were stimulated for 4 h with M. stadtmanae , M. smithii , or the TLR8 agonist TL8-506 (1 μg/mL), with or without pre-treatment using the TLR8 inhibitor CU-CPT9a. Expression levels of representative Class I and Class II genes were measured by RT-qPCR and normalized to the housekeeping gene HPRT . Data are presented as fold induction relative to unstimulated controls. Each data point represents an individual donor ( n = 3); bars indicate mean ± SD. Statistical significance between paired conditions was assessed using a two-tailed paired t -test. b Volcano plots were generated from RNA-seq data of PBMC-derived monocytes using Sleuth. For each condition, log 2 FC (x-axis) was plotted against –log 10 p -value (y-axis). The inhibitor only, M. stadtmanae and M. smithii groups were compared to the unstimulated control, while the M. stadtmanae + inhibitor and M. smithii + inhibitor groups were compared to the inhibitor-only control. Red dots represent upregulated DEGs genes, blue dots represent downregulated DEGs genes, and gray dots denote non-significant changes. The five most upregulated and five most downregulated genes (by log 2 FC) are labeled. Total numbers of DEGs for each comparison are indicated in boxed annotations. c The 3D PCA plot displays the first three principal components (PC1, PC2, and PC3), which capture the major sources of variance in the dataset. Samples are color-coded by experimental condition: unstimulated control, TLR8 inhibitor only, M. smithii (4 h), M. stadtmanae (4 h), M. smithii (4 h) + inhibitor, and M. stadtmanae (4 h) + inhibitor. d A Venn diagram illustrates the overlap of upregulated DEGs in response to 4 h stimulation with M. smithii or M. stadtmanae , with or without TLR8 inhibitor treatment. e A dot plot shows paired log 2 FC of shared upregulated genes. Each dot represents a DEG detected under both M. stadtmanae and M. stadtmanae + TLR8 inhibitor conditions. The x-axis shows the log 2 FC under M. stadtmanae stimulation alone, and the y-axis shows the corresponding log 2 FC under inhibitor treatment. The long dashed diagonal line (y = x) indicates equal expression between conditions. Two additional short dashed lines, drawn parallel to the diagonal at ±1 log 2 FC difference, demarcate three groups: (1) blue dots, downregulated by inhibitor treatment (log 2 FC decrease ≥ 1); (2) gray dots, largely unaffected (difference between –1 and +1); and (3) red dots, increased by inhibitor treatment (log 2 FC increase ≥ 1).

Article Snippet: The chemically synthesized TLR8 compound ligand TL8-506 (InvivoGen) was used at a concentration of 1 μg/mL.

Techniques: Derivative Assay, Expressing, Quantitative RT-PCR, Two Tailed Test, Generated, RNA Sequencing, Control, Labeling, Comparison

a Heatmap displaying the expression in PBMC-derived monocytes stimulated for 4 h with M. stadtmanae or M. smithii , with or without TLR8 inhibitor (CU-CPT9a). RNA-Seq data are shown for three individual donors (n = 3). The left panel shows a heatmap of log 2 -transformed, normalized expression of the top 100 most variable genes. The right panel displays a sample-to-sample correlation heatmap based on Pearson correlation calculated from the 100 most variable genes on the left. Clustering uses as distances 1 – correlation. b Heatmap displaying the normalized expression levels of Class I and Class II genes (in PBMC-derived monocytes) across individual donors (n = 3), based on transcriptome sequencing data. c Bubble plots depict the top ten enriched pathways for two subsets of genes identified at 4 h after M. stadtmanae stimulation that were not downregulated by TLR8 inhibition. Bubble size indicates the number of genes associated with each term, and bubble color reflects the adjusted p -value (FDR) of enrichment significance.

Journal: bioRxiv

Article Title: Differential methanogenic archaea-induced TLR8-dependent signaling is governed by NF-κB p65- and STAT1/2-controlled gene classes

doi: 10.1101/2025.09.30.679018

Figure Lengend Snippet: a Heatmap displaying the expression in PBMC-derived monocytes stimulated for 4 h with M. stadtmanae or M. smithii , with or without TLR8 inhibitor (CU-CPT9a). RNA-Seq data are shown for three individual donors (n = 3). The left panel shows a heatmap of log 2 -transformed, normalized expression of the top 100 most variable genes. The right panel displays a sample-to-sample correlation heatmap based on Pearson correlation calculated from the 100 most variable genes on the left. Clustering uses as distances 1 – correlation. b Heatmap displaying the normalized expression levels of Class I and Class II genes (in PBMC-derived monocytes) across individual donors (n = 3), based on transcriptome sequencing data. c Bubble plots depict the top ten enriched pathways for two subsets of genes identified at 4 h after M. stadtmanae stimulation that were not downregulated by TLR8 inhibition. Bubble size indicates the number of genes associated with each term, and bubble color reflects the adjusted p -value (FDR) of enrichment significance.

Article Snippet: The chemically synthesized TLR8 compound ligand TL8-506 (InvivoGen) was used at a concentration of 1 μg/mL.

Techniques: Expressing, Derivative Assay, RNA Sequencing, Transformation Assay, Sequencing, Inhibition

M. stadtmanae (left) is taken up more efficiently than M. smithii (right), resulting in stronger delivery of archaeal RNA to endosomal TLR8. This high-intensity signal robustly activates NF-κB (p65) and STAT1/2 pathways, inducing both Class I and Class II gene programs. In contrast, the weaker uptake of M. smithii limits TLR8 engagement and p65-dependent activation, leading to reduced induction of Class I genes. However, Class II genes, which require a lower activation threshold and depend on STAT1/2, remain largely preserved. This model suggests that Class I activation requires sufficient occupancy of multiple p65 binding sites, explaining why low-intensity signaling fails to induce these genes, whereas STAT1/2-driven Class II programs can be triggered without such extensive binding. Together, the model illustrates that Class I programs are threshold-dependent, whereas Class II programs can be triggered under lower TLR8 signaling conditions.

Journal: bioRxiv

Article Title: Differential methanogenic archaea-induced TLR8-dependent signaling is governed by NF-κB p65- and STAT1/2-controlled gene classes

doi: 10.1101/2025.09.30.679018

Figure Lengend Snippet: M. stadtmanae (left) is taken up more efficiently than M. smithii (right), resulting in stronger delivery of archaeal RNA to endosomal TLR8. This high-intensity signal robustly activates NF-κB (p65) and STAT1/2 pathways, inducing both Class I and Class II gene programs. In contrast, the weaker uptake of M. smithii limits TLR8 engagement and p65-dependent activation, leading to reduced induction of Class I genes. However, Class II genes, which require a lower activation threshold and depend on STAT1/2, remain largely preserved. This model suggests that Class I activation requires sufficient occupancy of multiple p65 binding sites, explaining why low-intensity signaling fails to induce these genes, whereas STAT1/2-driven Class II programs can be triggered without such extensive binding. Together, the model illustrates that Class I programs are threshold-dependent, whereas Class II programs can be triggered under lower TLR8 signaling conditions.

Article Snippet: The chemically synthesized TLR8 compound ligand TL8-506 (InvivoGen) was used at a concentration of 1 μg/mL.

Techniques: Activation Assay, Binding Assay

Review

tlr8 agonist (InvivoGen)

Structured Review

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1) Product Images from "Let-7b-5p differentially regulates human first trimester trophoblast migration and sFlt-1 through TLR7 and TLR8"

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