Fig. 6. The TREM2-AR axis correlates with poor prognosis and promotes cancer progression and blockade of the TREM2-AR axis improves the efficacy of anti-PD1 therapy in prostate cancer.

a Box plot depicting AR (left), TREM2 (medium) and APOE (right) expression in TCGA bulk RNA-seq samples of human normal prostate (n = 152 biologically independent samples) and prostate cancer samples (PRAD, n = 492 biologically independent samples) from GEPIA database. Box plots show the median (centre line), 25th and 75th percentiles (box bounds), and whiskers extend to the 5th and 95th percentiles which represent minima and maxima. b Disease-free survival based on AR, TREM2 and APOE expression in primary prostate tumours (TCGA) from GEPIA database. the High AR (left) /TREM2 (medium) /APOE (right) group (red) (n = 246 biologically independent samples) corresponds to the first 50% of expression, and the Low AR (left) /TREM2 (medium) /APOE (right) group (blue) (n = 246 biologically independent samples) corresponds to the last 50% of expression. c Experimental scheme. Created in BioRender. Qiaohua, W. (2025) https://BioRender.com/ly3agho. C57BL/6 TREM2^f/f and TREM2^f/f-Lyz2-cre mice were subjected to subcutaneous injections of RM1-Luc cells in the inguinal region. Surgical castration (CTX) was performed after 3 days. ENZA treatment commenced on day five. Mice were euthanized on day 15 for analysis and data collection. The sham group for each genotype serves as its own control. RM1-Luc: luciferase-tagged RM1, s.c.: subcutaneous, CTX: Castration, ENZA: Enzalutamide. d−f Representative prostate tumour size (n = 5 mice) (d), tumour weight (n = 6 mice) (e), and tumour growth curve (n = 5 mice) (f) of each group. g The proportion of CD45⁺CD11b⁺F4/80⁺ macrophages in the tumour were quantified by flow cytometry (n = 5 mice). h The proportion of CD11b⁺F4/80⁺CD206⁺ (left) macrophages and CD11b⁺F4/80⁺CD86⁺ (right) macrophages in the tumour were quantified by flow cytometry (n = 5 mice). i ELISA assay was employed to quantify the protein levels of IL-10 and TGF-β in the tumour griding supernatant of tumour-bearing mice (n = 5 mice). j The proportion of CD45⁺CD3⁺CD8⁺ T cells in the tumour was quantified by flow cytometry (n = 5 mice). k The number of PD1⁺CD8⁺ T cells mg^-1 in the tumour (n = 5 mice). l The number of IFN-γ⁺CD8⁺ T cells mg^-1 (left) and TNF⁺CD8⁺ T cells mg^-1 (right) in the tumour (n = 5 mice). m The proportion of granzyme B (left) and perforin (right) in the intraprostatic CD8⁺ T cells of tumour-bearing mice (n = 5 mice). (n) Experimental scheme. Created in BioRender. Qiaohua, W. (2025) https://BioRender.com/ly3agho. C57BL/6 TREM2^f/f and TREM2^f/f-Lyz2-cre mice were subjected to subcutaneous injections of RM1 cells in the inguinal region. Surgical castration (CTX) was performed after 3 days. ENZA and anti-PD1 treatment commenced on day five. Mice were euthanized on day 15 for analysis and data collection. o, p Representative prostate tumour size (n = 6 mice) (o), and tumour weight (n = 6 mice) (p) of each group. All the data are presented as mean ± SD. The P-values were determined by two-sided Mann-Whitney U test for (a); by Log-rank (Mantel-Cox) test for (b); by two-way ANOVA with Tukey’s multiple comparisons for (f); and by one-way ANOVA with Tukey’s multiple comparisons for (e, g−m, p). Source data are provided as a Source Data file.