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Fig. 6 | Journal of Experimental & Clinical Cancer Research

Fig. 6

From: Determinants of resistance to VEGF-TKI and immune checkpoint inhibitors in metastatic renal cell carcinoma

Fig. 6

Resistance to ICI therapy. Various putative or acquired immune escape mechanisms can result in tumour evading the immune checkpoint inhibitor therapy. These include; a) Lack of T cell priming through impaired antigen presentation via inadequate DC maturation or through appropriate MHC1 expression; b) decreased T cell activity in the tumour microenvironment through increased infiltration of Tregs, expression of T cell suppressive molecules on tumour cells such as IDO, PD-L1, or mutational changes in JAK2 pathway, loss of tumour suppressor genes such as PTEN or increased expression of T cell exhaustion markers such as TIM-3, PD-1, etc.; c) lack of T cell infiltration in the tumour microenvironment due to enhanced LDH accumulation, low expression of T cell migratory chemokines, increased expression of tumour suppressive cytokines such as TGF-β, IL-6, IL-8, etc.

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