Frontiers in immunology
Tumor-associated macrophages in the tumor immune microenvironment of non-small cell lung cancer
By Saldana SFA, Abdulrab ND and Raza A.
Abstract
Background
Non-small cell lung cancer (NSCLC) remains the leading cause of cancer mortality, and resistance to immune checkpoint inhibitors (ICIs) is largely driven by the tumor immune microenvironment (TIME), in which tumor-associated macrophages (TAMs) are major regulators.
Objectives
This review summarizes recent advances in understanding TAM heterogeneity, their contribution to immune resistance in NSCLC, and emerging therapeutic strategies targeting TAMs.
Methods
A literature search was conducted using PubMed and Google Scholar, focusing on studies published between 2021 and 2025. Key search terms included "non-small cell lung cancer", "tumor immune microenvironment", "macrophage heterogeneity", "M1 macrophages", "M2 macrophages", "SPP1+ macrophages", "TREM2+ macrophages", "immune checkpoint inhibitor resistance", "macrophage metabolic reprogramming", and "TAM-targeted therapies". Relevant studies addressing TAM heterogeneity, immune resistance, metabolic and molecular regulation, and therapeutic targeting in NSCLC were prioritized, while earlier studies were included where necessary to provide mechanistic context.