Natural killer cells
Natural killer cells (NK) are lymphocytes of the innate immune system that monitor cell surfaces of autologous cells for an aberrant expression of major histocompatibility complex class I (MHC I) molecules and cell stress markers, which play an important role in antitumor immune responses[72]. The study found that patients with high expression of NK cells had a greater OS and PFS and NK cells increased after EGFR-TKIs treatment[73]. For EGFR-TKIs resistant lung cancer, up regulating ICAM1 can induce drug resistance, and NK92-CD16 cells combined with the EGFR antibody could reverse the drug resistance[74]. Another study found that gefitinib greatly enhanced NK cells cytotoxicity to lung cancer cells with EGFR L858R+T790M resistance mutation. Gefitinib could block the immune escape by up-regulating the expression of NKG2D ligands ULBP1, ULBP2, or MICA on tumor cells and NKG2D on NK cells in the co-culture system[75]. A combination of EGFR-TKIs and NK cells adoptive immunotherapy may represent a potentially effective strategy for EGFR-TKIs resistant lung cancer.