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.