The prognostic impact of tumor-associated macrophages and intra-tumoral apoptosis in non-small cell lung cancer

Abstract

Summary. Lung cancer is the leading cause of cancerrelated deaths worldwide. Non-small cell lung cancer (NSCLC) accounts for 80% of all lung malignancies. Tumor-associated macrophages (TAM) are abundant components of NSCLC. Although under certain conditions TAM can kill tumor cells, they can also act as tumor promoters secreting a variety of factors that directly stimulate tumor invasion and metastasis. TAM presents two distinct phenotypes: the classically activated (or M1) phenotype, which is highly proinflammatory (phagocytic and cytotoxic), and the alternatively activated (or M2) phenotype, which has anti-inflammatory and pro-tumoral properties. The polarization status of TAM depends on stimulating factors from the tumor microenvironment, and some in vitro evidence implies that the phagocytosis of apoptotic bodies derived from tumoral cells is a key factor in M1/M2 modulation, raising the question of whether the evaluation of the apoptotic index (AI) and macrophage polarization have a prognostic role in NSCLC patient survival. The present article systematically reviewed the published series of clinical data that correlated the AI and/or macrophage densities and polarization status (M1/M2) with the outcome of non-small cell lung cancer patients. Even though an overwhelming body of clinical data support that TAM’s density, micro-anatomical localization, phenotype and intra-tumoral AI are independent predictors of survival time, no study to date has been conducted to evaluate the impact of these parameters altogether in NSCLC patient outcome. Joint analysis of these biologic factors in future studies might reveal their prognostic value in the management of NSCLC cases.