Journal: bioRxiv

Article Title: A class act: HDAC1- Malat1 regulates MDSC apoptosis and cell cycling to decrease suppression of T cells

doi: 10.64898/2026.03.23.713743

Figure Lengend Snippet: (A) UMAP visualization of major cell clusters identified from single cell RNA sequencing (scRNA-seq) of NT2.5-LM breast-to-lung metastatic tumors after 3 weeks of treatment with: vehicle (V), Entinostat (E), anti-CTLA-4 + anti-PD-1 immune checkpoint inhibitors (PC), and Entinostat + anti-CTLA-4 + anti-PD-1 combination (EPC). Subclusters of MDSCs identified: G-MDSCs and M-MDSCs. (B) Iterative logistic regression analyses conducted on the major MDSC cluster comparing the Vehicle (V) and Entinostat + ICIs combination treatment (EPC). (C) Expression of Malat1 / MALAT1 in G- and M-MDSCs isolated from lung metastases of NT2.5-LM mice treated with vehicle vs. Entinostat for 3 weeks (left, n=2 from 5 pooled mice per treatment group), J774M murine MDSC-like cell line treated with Entinostat for 24 hours (middle, n=3), and human PBMC-derived MDSCs (hMDSCs) treated with Entinostat for 24 hours (right, n=3). (D) Median Fluorescence Intensity expression of Malat1 in CD45 + CD11b + MHC-II - F4/80 - Ly6G - Ly6C hi cells from lung metastases in 4T1 mice, treated with vehicle (V), Entinostat (E), and Entinostat + ICIs (EPC) for 3 weeks. (E) Expression of Malat1 in J774M cell line treated with various concentrations of various HDAC inhibitors, with corresponding targeted class and specific HDACs. One-way ANOVA for (C, E: all statistically significant with p<0.05, unless indicated as non-significant (ns)), Kruskal-Wallis test with Dunn’s correction for (D). * p<0.05, *** p< 0.001, **** p<0.0001. ENT = Entinostat; PAN = Panobinostat; BEL = Belinostat; VOR = Vorinostat; TSA = Trichostatin A; DOM = Domatinostat; CHL = Chlopynostat; PYR = Pyroxamide; SCA = Santacruzamate A; RGF = RGFP966; TMP = TMP269; SIS = SIS17.

Article Snippet: Immune checkpoint inhibitors (ICIs) used in this study: anti-CTLA-4 (BioXCell cat. #BE0131) and anti-PD-1 (BioXCell cat. #BE0146).

Techniques: Single Cell, RNA Sequencing, Expressing, Isolation, Derivative Assay, Fluorescence

Journal: bioRxiv

Article Title: A multivalent peptide-polymer conjugate material mimics STING to therapeutically activate innate immune signaling

doi: 10.64898/2026.03.24.712780

Figure Lengend Snippet: ( A ) Mice were inoculated with 3×10 6 BPPNM cells IP and dosed with 20 μg of STING or Scr conjugate delivered by LNP IP at 10, 13, 16, and 19 days after inoculation. Omental tumor was collected on day 20 for analysis by flow cytometry. Groups included N = 5 mice. ( B ) Cell populations in tumor after treatment, displaying percentage of CD45 + cells made up by T cells (CD3 + ), CD8 + T cells, CD4 + T cells, NK cells (CD3 - NK1.1 + ), B cells (CD19 + ), Macrophages (F4/80 + ), DCs (CD11c + MHCII + ), and MDSCs (CD11b + Gr-1 hi ). Percentage of CD45 - cells made up by BPPNM cancer cells (GFP + ) are also displayed. ( C-D ) Polarization of Macrophages (F4/80 + ), showing MFI and representative distributions of ( C ) CD86 and ( D ) CD206. ( E ) Activation of DCs (CD11c + MHCII + ), showing MFI and representative distributions of CD86. ( F ) Expression of PD-1 on CD8 + T cells, showing percentage of cells that are PD-1 + and representative distributions of PD-1. P values computed with a one-way ANOVA followed by Tukey’s post-hoc test are displayed above each figure. All flow data is represented as mean ± SD. ( G ) Mice were inoculated with 3×10 6 BPPNM cells IP and dosed with 20 μg of STING or Scr conjugate delivered by LNP IP at 10, 13, 16, 19, and 22 days after inoculation. A subset of groups were additionally treated with 100 μg αPD-1 antibody at 11 and 17 days after inoculation. Groups included N = 6 (PBS, STING LNP, Scr LNP), N = 5 (STING LNP + αPD-1), or N = 4 (PBS + αPD-1, Scr LNP + αPD-1) mice. ( H ) Survival plot with P values determined by log(rank) (Mantel–Cox) test. ( I-K ) Tumor burden measured by IVIS, displaying ( I ) geometric mean ± SD bioluminescent intensity over the treatment period, ( J ) an image of the mouse with the median bioluminescent intensity from each group at the measurement following the end of treatment (day 24), and ( K ) individual mouse bioluminescent intensity values.

Article Snippet: In groups specified in figure captions, mice were also administered a 100 μg dose of anti-mouse PD-1 antibody (Bio X Cell #BE0273 InVivoMAb, Clone 29F.1A12) in 200 μL of 1× PBS on days 11 and 17 after tumor inoculation.

Techniques: Flow Cytometry, Activation Assay, Expressing

Journal: bioRxiv

Article Title: Anti-CSF-1R therapy with combined immuno- chemotherapy coordinate an adaptive immune response to eliminate macrophage enriched Triple Negative Breast Cancers

doi: 10.1101/2025.04.30.651522

Figure Lengend Snippet: (A) Schematic illustration of short-term treatment regimen. T12 tumor cells are first injected via TV into female Balb/c mice. Post 19-day TV injection the mice were randomized and considered to be day 0. IgG control, CTX and SNDX-ms6352 were administered i.p. at day 0 and day 7, anti-PD1 and its IgG2a isotype control were administered every 2 days. (B) Mouse body weight (g) following short-term treatment of IgG Control, SNDX-ms6352, CTX, CTX+SNDX-ms6352 and CTX+SNDX-ms6352+aPD1 in T12 GEMMs with established lung metastases. Statistical analysis was performed using Two-way ANOVA and Tukey’s multiple comparisons test ( n = 5 mice per treatment). (C) Quantification of lung metastases post short-term treatment. Serial sectioning was performed to collect a total of 10 sections for each sample. Metastases with sizes of <1 mm, 1-3 mm, 3-5 mm, and >5 mm were assigned scores of 1, 2, 3, and 4, respectively. Significance determined by Two-way ANOVA and Tukey’s multiple comparisons test. (D) Representative H&E staining of lung metastases at day 7 post IgG control, SNDX-ms6352, CTX, CTX+SNDX-ms6352 and CTX+SNDX-ms6352+aPD1 treatments ( n = 5 mice per treatment). (E) Imaging mass cytometry analysis post IgG control, SNDX-ms6352, CTX, CTX+SNDX-ms6352 and CTX+SNDX-ms6352+aPD1 treated T12 GEMMs at day 7. Clustered and individual channels include Vimentin, CD44, F4/80, S100A8, PD-L1, Ki67, and 191ir (DAPI) markers. (F) Median distance of immune cells from tumor cells post IgG control, SNDX-ms6352, CTX, CTX+SNDX-ms6352 and CTX+SNDX-ms6352+aPD1 treated T12 GEMMs at day 7, distance analysis is representative from IMC analysis of individual channels CD8, CD4, S100A8/9 and F4/80. Significance was determined using Two-way ANOVA and Tukey’s multiple comparisons tests ( n = 3 ROI). (G) Median expression levels of the exhaustion markers PD-L1 and PD-1 post IgG control, SNDX-ms6352, CTX, CTX+SNDX-ms6352 and CTX+SNDX-ms6352+aPD1 treated T12 GEMMs at day 7. P -values were generated using diffcyt function (type of analysis, DS; method for DS testing, diffcyt-DS-limma). P -values were then adjusted using the Benjamini-Hochberg method ( n = 3 ROI). (H) Illustration depicting pro-tumor immunosuppressed and anti-tumor, tumor killing phenotypes. Phenotypes are representative of the proximity between TAMs, CD4, CD8, S100A/9 Neutrophils within tumor cells. Data shown as mean ±SEM. For all panels * P < 0.05; ** P < 0.01; *** P < 0.001; **** P < 0.0001.

Article Snippet: For ICB treatment, mice were administered RecombiMab anti-mouse PD1 (BioXcell, CD279, CP151) and RecombiMAb anti-mouse IgG2a isotype (BioXcell, CP150) 200 µg per mouse every three days via i.p. injection .

Techniques: Injection, Control, Staining, Imaging, Mass Cytometry, Expressing, Generated