Fig. 7: Administration of miR-29b-3p resensitized KRAS-mutated CRC to radiotherapy and ICBs.

A The subset of tumor-infiltrating CD86⁺ DC cells (CD86⁺CD11c⁺MHCII⁺ CD45⁺7AAD^-) within primary tumors was analyzed by flow cytometric analysis (n = 3). One-way ANOVA t test. *p < 0.05. B The subset of tumor-infiltrating CD80⁺ DC cells (CD80⁺CD11c⁺MHCII⁺ CD45⁺7AAD^-) within primary tumors was analyzed by flow cytometric analysis (n = 3). One-way ANOVA t test. *p < 0.05. C The subset of tumor-infiltrating CD4⁺ cells (CD4⁺CD3⁺CD45⁺7-AAD^-) and CD8⁺ cells (CD8⁺CD3⁺CD45⁺7-AAD^-) within primary tumors was analyzed by flow cytometric analysis (n = 3). One-way ANOVA t test. *p < 0.05. D The subset of tumor-infiltrating effector/memory CD4 T_EM cells (CD44⁺CD62L^-CD4⁺CD3⁺CD45⁺7-AAD^-) within primary tumors was analyzed by flow cytometric analysis (n = 3). One-way ANOVA t test. *p < 0.05. E The subset of tumor-infiltrating effector/memory CD8 T_EM cells (CD44⁺CD62L^-CD8⁺CD3⁺CD45⁺7-AAD^-) within primary tumors was analyzed by flow cytometric analysis (n = 3). One-way ANOVA t test. *p < 0.05. F The subset of tumor-infiltrating IFNγ⁺CD8⁺ lymphocytes (IFNγ⁺CD8⁺CD3⁺CD45⁺7-AAD^-) within primary tumors was analyzed by flow cytometric analysis (n = 3). One-way ANOVA t test. *p < 0.05. G CT26 cells were inoculated into right hind leg (2 × 10⁵ cells) by subcutaneous injection. On Day 9 and 10, local tumors in right hind leg were irradiated with 5 Gy. AAV-Vec. and AAV-pre-mmu-miR29b (1 × 10⁸ vg/mouse) was intramuscular injected on Day 4, 9, 14 and 18. Anti-mouse CD8 or PD-1 antibodies were intraperitoneal injected on Days 10, 15, 20 and 25. The tumor volume was measured every 3 days (n = 5-6). Two-way ANOVA t test. *p < 0.05, **p < 0.01 and ***p < 0.001. H The proposed mechanism of oncogenic KRAS-mediated miR-29b-3p/DNMT3b/STING pathway to attenuate RT response in KRAS-mutated CRC.