Journal: Frontiers in Immunology

Article Title: UPF1-dependent glycolysis driven by LINC00887 facilitates macrophage M2 polarization in clear cell renal cell carcinoma

doi: 10.3389/fimmu.2026.1833383

Figure Lengend Snippet: Overexpression of UPF1 in ccRCC inhibits M2 macrophage polarization and enhances the tumor suppressor function of CD8 + T cells, Caki-1 cell groups of sh-NC+PBS, sh-UPF1+PBS, or sh-UPF1 + 2-DG, and the conditioned medium was used to culture and polarize M0 macrophages. The polarized macrophages were cultured with activated CD8 + T cells. (A) CFSE assessed CD8 + T cell proliferative capacity. (B) Flow cytometry measured apoptosis rate of CD8 + T cells in different co-culture systems. (C) CD8 + T cells from culture systems were co-cultured with normal Caki-1 cells, with LDH assays determining cytotoxic effect of CD8 + T cells. *, p < 0.05. cRCC, Clear cell renal cell carcinoma; UPF1, Up-frameshift protein 1; 2-DG, 2-Deoxy-D-glucose; CFSE, Carboxyfluorescein succinimidyl ester.

Article Snippet: Primary CD8 + Cytotoxic T Cells (PCS-800-017) were from ATCC (USA).

Techniques: Over Expression, Cell Culture, Flow Cytometry, Co-culture Assay

Journal: Frontiers in Immunology

Article Title: UPF1-dependent glycolysis driven by LINC00887 facilitates macrophage M2 polarization in clear cell renal cell carcinoma

doi: 10.3389/fimmu.2026.1833383

Figure Lengend Snippet: LINC00887/UPF1-mediated aerobic glycolysis leads to lactic acid accumulation and facilitates immune evasion in ccRCC in vivo , A syngeneic tumor model was developed by injecting BALB/c mice with Renca cells expressing sh-NC or sh-LINC00887, followed by treatment with sh-NC or sh-UPF1 lentivirus. A-C: Assessment of tumor size (A) , volume (B) , and weight (C) . (D, E) qRT-PCR analyses for LINC00887 (D) and UPF1 (E) mRNA levels. (F) IHC analysis for UPF1, LDH-A, KI67 protein levels. (G) Kit assay for lactate levels in tumors. (H) Proportion of M2 macrophages (F4/80+CD206+) by flow cytometry. (I) Immunofluorescence assay for CD206+ macrophages. (J) Proportion of CD8 + T cells (CD3 + CD8 + ) in tumor tissues. ns, no significant difference. * p < 0.05. cRCC, Clear cell renal cell carcinoma; UPF1, Up-frameshift protein 1; LDH-A, Lactate dehydrogenase A; CD206, Mannose receptor C-type 1; CD3, Cluster of differentiation 3; CD8, Cluster of differentiation 8.

Article Snippet: Primary CD8 + Cytotoxic T Cells (PCS-800-017) were from ATCC (USA).

Techniques: In Vivo, Expressing, Quantitative RT-PCR, Analysis, Flow Cytometry, Immunofluorescence

Journal: Nature Communications

Article Title: p38α orchestrates BRAF V600E -melanoma progression and immunotherapy response via tumor fitness and immune microenvironment modulation

doi: 10.1038/s41467-026-77868-4

Figure Lengend Snippet: Quantification of ( a ) upregulated and ( b ) dowregulated cytokines in untreated VHMM109 and VHMM203 cells ( n = 2 independent experiments in duplicates). c Differentialy regulated cytokines in VHMM109 and VHMM203 cells following IFNγ treatment ( n = 2 independent experiments in duplicates). d Immunoblot showing the p38 expression on B ( n = 6) and B ; p38α ( n = 4) tumor-derived cell lines. Gene expression scores (RT-qPCR) were calculated as the mean expression values across all cell lines within each genotype ( B , n = 6); B ; p38α n = 4), see Supplementary Fig. ) and treatment. e Schematic of the experimental design for T cell phenotyping. Created in BioRender. Recio, J. (2026) https://BioRender.com/yx7nwa6 and https://BioRender.com/vxmo93e ). Frecuencies of CD8 + T cells subsets CD69 + , CD44 + ;CD62L + (TM/CM), CD44 + ;CD62L - (TE/EM) and PD-1 + ;TIM-3 + ;CD44 + ;CD62L - (exhausted TE/EM) are shown below ( n = 3 independet experiments). f Schematic of the experimental design for tumor cell killing assay (Created in BioRender. Recio, J. (2026) https://BioRender.com/x4pswf9 and https://BioRender.com/vxmo93e ). Left, fold change in tumor cell death according to the genotype. Right, fold chage in tumor cell death in VHMM109 and VHMM203 cells following the indicated treatments OT-I (addition of CD8 OT-I cells), neflamapimod (Nefl.), pexmetinib (Pex.), ralimetinib (Rali.) is showed ( n = 3 independet experiments). g In vivo tumor growth of the indicated syngeneic cell lines following CD8⁺ T-cell or NK-cell depletion ( n = 5 mice per group, 2 independet experiments). Treatment schedules are shown in the schematics above the graphs (Created in BioRender. Recio, J. (2026) https://BioRender.com/61paqxv and https://BioRender.com/x4pswf9 ). h Scheme outlining the experimental design to assess tumor infiltration and response to adoptive cell transfer (ACT) of pre-activated OT-I effector T cells in VHMM203-OVA ( B ; p38α ) tumors (Created in BioRender. Recio, J. (2026) https://BioRender.com/sw0hszd ). Graphs show tumor growth following ACT in B ; p38α -OVA tumors; the arrow indicates the day of ACT ( n = 5 mice per group). The experiment was performed twice. Bar graphs depict the mean ± SD. Statistical analysis was performed using using a two-tailed Studet’s t test ( a–c, e, f ), one-way ANOVA with Tukey’s multiple comparisons test ( d ) or two-tailed Mann-Whitney-Wilcoxon test ( g, h ) ± SD. e–h Schematic of cells created in BioRender. Recio, J. (2026) https://BioRender.com/yx7nwa6 .

Article Snippet: Naïve CD8 + T cells were isolated from spleens from donor OT-I mice (C57BL/6- Tg ( TcraTcrb )1100Mjb) using the CD8 + T cell isolation kit (#130-104-075, Miltenyi Biotec) following the manufacturer’s instructions.

Techniques: Western Blot, Expressing, Derivative Assay, Gene Expression, Quantitative RT-PCR, In Vivo, Analysis, Two Tailed Test, MANN-WHITNEY, FACS, Co-Culture

Journal: Nature Communications

Article Title: p38α orchestrates BRAF V600E -melanoma progression and immunotherapy response via tumor fitness and immune microenvironment modulation

doi: 10.1038/s41467-026-77868-4

Figure Lengend Snippet: a Schematic of the in vivo treatment design with αPD-1 and αTIM-3. Created in BioRender. Recio, J. (2026) https://BioRender.com/x4pswf9 . b Tumor growth curves of YUMMER1.7 and VHMM212 tumors treated with αPD-1, αTIM-3, or their combination. Dashed lines indicate individual tumors. Representative endpoint tumor images are shown; scale bars, 1 cm. ( n = 8 mice per group). c Mean tumor volumes for both cell lines under the indicated treatments; dots represent individual tumors ( n = 8 mice per group). Percentages of ( d ) CD3⁺, ( e ) CD4⁺, ( f ) CD8⁺, and NK1.1⁺ cells among intratumoral CD45⁺ cells from whole tumors across treatments ( n = 5 tumors except for VHMM212 treated with αTIM3 n = 3 and αPD1 + αTIM3 n = 3). g Immunoblots showing the expression of the indicated proteins in YUMMER1.7 and VHMM212 tumors ( n = 3) and different group of treatments. h Schematic of the in vivo treatment design with αPD-1 and p38 inhibitors. Created in BioRender. Recio, J. (2026) https://BioRender.com/x4pswf9 . i Tumor growth curves of YUMMER1.7 tumors treated with αPD-1, neflamapimod (Nefl.), pexmetinib (Pex.), or their combinations with αPD-1. Dashed lines indicate individual tumors ( n = 16). j Waterfall plot of tumor responses classified as stable disease (SD, ≤20% increase or <30% reduction), partial response (PR, ≥30% reduction), or complete response (CR, complete disappearance; volume = 0). k Representative endpoint tumor images are shown (scale bars, 1 cm). Tumor weights from individual samples under different treatments are presented on the right ( n = 16). l Body weight changes of mice across treatment groups ( n = 16). Bar graphs depict the mean ± SD. Statistical analysis was performed using the two-tailed Mann-Whitney-Wilcoxon test ( b ), one-way ANOVA with Tukey’s multiple comparisons test ( d–f, i ) or a two-way repeated-measures ANOVA with treatment and time as factors, followed by Tukey’s multiple-comparison test ( c, k, l ).

Article Snippet: Naïve CD8 + T cells were isolated from spleens from donor OT-I mice (C57BL/6- Tg ( TcraTcrb )1100Mjb) using the CD8 + T cell isolation kit (#130-104-075, Miltenyi Biotec) following the manufacturer’s instructions.

Techniques: In Vivo, Western Blot, Expressing, Analysis, Two Tailed Test, MANN-WHITNEY, Comparison

Journal: Nature Communications

Article Title: p38α orchestrates BRAF V600E -melanoma progression and immunotherapy response via tumor fitness and immune microenvironment modulation

doi: 10.1038/s41467-026-77868-4

Figure Lengend Snippet: a Volcano plot of good-response common genes (Supplementary Fig. – ). Highlighted in red are genes upregulated in B ; p38α ( n = 3) versus B tumors ( n = 5). b Scoring of the p38α-associated signature (top nine expressed genes, log₂FC > 0.5, n = 8) in RNA-expression data from Fig. . Differential expression was assessed using the limma package with moderated t -tests and adjusted p -values. ( a , b ). c Survival matrix from the Tumor Immunotherapy Gene Expression Resource (TIGER, http://tiger.canceromics.org ) showing predictive good (blue) or poor (red) responses of various gene signatures, including the p38α-associated signature, across melanoma studies of immune checkpoint inhibitor (ICI) or adoptive cell therapy (ACT) responses. CAF cancer-associated fibroblasts, GEP gene expression profile, TAM tumor-associated macrophages, IFNG interferon gamma, TLS tertiary lymphoid structure, MDSC myeloid-derived suppressor cells. d Expression of MAPK14 or the p38α-associated signature in non-responders (NR, n = 27) and responders (R, n = 23) to αPD-1 treatment (study: PRJEB23709) along with associated survival curves for patients with high versus low MAPK14 or p38α-signature expression. Data are presented as box plots showing the median (horizontal line), interquartile range (box 25th–75th percentiles), and individual observations (points). Whiskers indicate the range of values within 1.5 × IQR Statistical significance was assessed using the Wilcoxon rank-sum test. e Schematic summary created in BioRender. Recio, J. (2026) https://BioRender.com/x4pswf9 : Loss of p38α in tumor cells enhances anti-tumor immunity, with increased T memory/central memory cells, higher CD8⁺ T cell exhaustion, greater NK and NK-T cell activity, fewer macrophages (particularly M2-type), a shift from monocytic to polymorphonuclear MDSCs, and reduced dendritic cell activation, resulting in a less immunosuppressive tumor environment.

Article Snippet: Naïve CD8 + T cells were isolated from spleens from donor OT-I mice (C57BL/6- Tg ( TcraTcrb )1100Mjb) using the CD8 + T cell isolation kit (#130-104-075, Miltenyi Biotec) following the manufacturer’s instructions.

Techniques: RNA Expression, Quantitative Proteomics, Gene Expression, Derivative Assay, Expressing, Activity Assay, Activation Assay, Significance Assay