Dendritic cells
Dendritic cells (DC) are unique immune cells linking innate and adaptive immune responses. They are considered as the most effective antigen presenting cells, which play an important role in the process of tumor antigen recognition and presentation[68]. It was found that the level of major histocompatibility complex class II (MHC II) positive DC in EGFR-TKIs sensitive tumor was higher than that in EGFR-TKIs resistant tumor[69]. Another study found that lung cancer with EGFR mutation inhibited the maturation of DC and induced the production of anergic DC to repress antitumor immunity through exosomes[70]. Analysis of the NSCLC transcriptomic dataset revealed selective overexpression of CD47 in patients with EGFR mutation. EGFR-TKIs significantly reduced CD47 expression on the surface of pre-apoptotic cells, favoring more efficient engulfment of cancer cells by DC. CD47 expression became up-regulated following EGFR-TKIs resistance development, and blocking of this protein by a specific monoclonal antibody increased the clearance of EGFR-TKI resistant cells by phagocytes[71]. Therefore, EGFR-TKIs resistance is associated with decreasing of DC and malfunction of DC.