A narrative review of tumor-associated macrophages in lung cancer: regulation of macrophage polarization and therapeutic implications

Abstract

Lung cancer is the deadliest malignancy worldwide. An inflammatory microenvironment is a key factor contributing to lung tumor progression. Tumor-Associated Macrophages (TAMs) are prominent components of the cancer immune microenvironment with diverse supportive and inhibitory effects on growth, progression, and metastasis of lung tumors. Two main macrophage phenotypes with different functions have been identified. They include inflammatory or classically activated (M1) and anti-inflammatory or alternatively activated (M2) macrophages. The contrasting functions of TAMs in relation to lung neoplasm progression stem from the presence of TAMs with varying tumor-promoting or anti-tumor activities. This wide spectrum of functions is governed by a network of cytokines and chemokines, cell-cell interactions, and signaling pathways. TAMs are promising therapeutic targets for non-small cell lung cancer (NSCLC) treatment. There are several strategies for TAM targeting and utilizing them for therapeutic purposes including limiting monocyte recruitment and localization through various pathways such as CCL2-CCR2, CSF1-CSF1R, and CXCL12-CXCR4, targeting the activation of TAMs, genetic and epigenetic reprogramming of TAMs to antitumor phenotype, and utilizing TAMs as the carrier for anti-cancer drugs. In this review, we will outline the role of macrophages in the lung cancer initiation and progression, pathways regulating their function in lung cancer microenvironment as well as the role of these immune cells in the development of future therapeutic strategies.