The role of tumor-associated macrophages in lung cancer: From mechanism to small molecule therapy

Tumor-associated macrophages (TAMs) are the main component of tumor-infiltrating immune cells in the lung tumor microenvironment. TAMs recruited to the lung cancer can create a suitable microenvironment for the growth and metastasis of lung cancer by secreting tumor promoting factors and interfering with the function of T cells. Currently, numerous studies have reported that small molecular drugs affect lung cancer progression by selectively targeting TAMs. The main ways include blocking the recruitment of monocytes or eliminating existing TAMs in tumor tissue, reprogramming TAMs into pro-inflammatory M1 macrophages or inhibiting M2 polarization of macrophages, interrupting the interaction between tumor cells and macrophages, and modulating immune function. Signaling pathways or cytokines such as CCL8, CCL2/CCR2, CSF-1/CSF-1R, STAT3, STAT6, MMPs, Caspase-8, AMPK α1, TLR3, CD47/SIRPα, have been reported to be involved in this process. Based on summarizing the role and mechanisms of TAMs in lung cancer progression, this paper particularly focuses on systematically reviewing the effects and mechanisms of small molecule drugs on lung cancer TAMs, and classified the small molecular drugs according to the way they affect TAMs. The study aims to provide new perspectives and potential therapeutic drugs for targeted macrophages treatment in lung cancer, which is of great significance and will provide more options for immunotherapy of lung cancer. •TAMs promote lung cancer growth, invasion, and metastasis via intricate mechanisms.•Small molecule drugs regulate TAMs recruitment or polarization to inhibit lung cancer.•Small molecules influence immune responses or TAM-tumor interactions to inhibit lung cancer.