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. 2022 Jun 10;23(12):6489. doi: 10.3390/ijms23126489

Figure 3.

Figure 3

Dynamic changes of tumor microenvironment (TME) of EGFR-mutated NSCLC during tyrosine kinase inhibitor treatment. TME of EGFR mutated adenocarcinoma is typically characterized by prevalence of M2 polarized macrophage, low levels of CD8+ cells, increased number of Treg, and upregulation of PD-L1. The latter, especially if associated with macrophage-mediated inflammation particularly through IL-6 and increased ROS levels, contributes to T-cell exhaustion. Additionally, several factors secreted by M2 polarized TAMs (as TGFbeta, TNFalpha, MMPs, VEGF, IL-8, bFGF, PGE2, CCL22, and CCL18). These factors contribute to tumor progression and immunodepression. The TKI treatment has been associated with a decrease in PD-L1 expression, lowering of Treg, and promotion of TAM polarization from M2 to M1 phenotype. Abbreviations: EGFR—epidermal growth factor receptor; NSCLC—non-small cell lung cancer; JAK—Janus Kinase; PI3K—phosphatidylinositol-3 kinase; NF-kB—nuclear factor-κB; IRF1—interferon regulatory factor 1; IL—interleukin; TAM—tumor-associated macrophages; MDCS—myeloid-derived suppressor cells; PD-L1—programmed death-ligand 1; ROS—reactive oxygen species; IFN—interferon; TKI—tyrosine kinase inhibitor; CSF1—colony stimulating factor 1; TGF—tumor growth factor; TNF—tumor necrosis factor; MMP—matrix metalloproteases; VEGF—vascular endothelial growth factor; PGE—prostaglandin E; CCL—C-C-motif ligand. Created with BioRender.com (https://biorender.com/, accessed on 17 May 2022).