Figure 2. Immune cells in TIME of EGFR mutant lung cancer.
The ratio of neutrophil, MDSC, CD68+ and CD204+ TAM(M2) in EGFR-TKIs sensitive lung cancer is less than that in EGFR-TKIs resistant lung cancer. However, the number of MHC II+DC and NK in EGFR-TKIs sensitive lung cancer is more than that in EGFR-TKIs resistant lung cancer. S100A9+MDSC transforms into M2 type TAM by activating RELB gene, and TAM(M2) induces EGFR-TKIs resistance through the NF-κB pathway. The EGFR-TKIs resistant lung cancer cell expresses CD47 which blocks the phagocytosis and antigen presentation of DC. Up regulating the expression of ULBP1,2, MICA on tumor cell and NKG2D on NK can promote NK cytotoxicity to tumor cell. B cell exists in the TLS which is associated with a good prognosis. B cell also differentiates into plasma cell and produces specific antibodies and recognizes tumor associated antigens. Breg can weaken the response of T cells and NK cells and facilitate the immune suppressive activity of regulatory T cells (Treg) by secreting immunosuppressive factors. The number of T cell like CD39+, CD8+ or PD-1+, TIM3+ T cell in EGFR mutant lung cancer is less than that in EGFR wild type lung cancer. T cell apoptosis was caused by EGFR mutation which increased the expression of PD-L1 through the p-ERK1/2/p-c-jun pathway. The number of Treg in EGFR mutant NSCLC was less than that in non-EGFR mutant NSCLC. The EGFR signal activates cJun/cJun N-terminal kinase and reduces interferon regulatory factor-1; the former increases CCL22, which recruits CD4+ regulatory T cells, and the latter decreases CXCL10 and CCL5, which induce CD8+ T cell infiltration. EGFR mutation also decreases the expression of MHC-I through the MEK-ERK pathway.