Tumor associated macrophages
Macrophage originates from progenitors in the bone marrow and enters the
peripheral blood. During homeostasis and inflammation, they migrate into
tissues and differentiate into macrophage following exposure to local
growth factors, proinflammatory cytokines, and microbial products. The
function of macrophages in the tumor is multiple[62]. As for tumor
associated macrophages (TAM), studies have found that the number of CD68
positive and CD204 positive TAM in EGFR mutant NSCLC tumor tissues is
less than that of EGFR wild type, and the prognosis is better[63].
Moreover, EGFR mutated lung cancer with high infiltrating CD204 positive
TAM had high aggressiveness and poor prognosis[64]. Another study
found that EGFR-TKIs resistant lung cancer was correlated to tumor
infiltrating CD68 positive TAM and S100A9 positive MDSC, which resulted
in resistance through the NF-κB pathway[65]. Two major macrophage
subpopulations with different functions include classically activated or
inflammatory (M1) and alternatively activated or anti-inflammatory (M2)
macrophages have been recognized. M1 macrophage has robust anti-tumoral
activity whereas M2 macrophage promotes tumor formation and
progression[66].CD68 positive and CD204 positive TAM is M2 type
macrophage. It was found that the level of M2 type macrophage in
EGFR-TKIs resistant lung cancer was higher than that in EGFR-TKI
sensitive lung cancer[67]. Therefore, it can be inferred that
EGFR-TKIs resistance is related to M2 type TAM, and reducing M2 type TAM
may reverse EGFR-TKIs resistance.