Remodeling the Tumor Immune Microenvironment by Traditional Chinese Medicine: Mechanisms Focusing on TAM Polarization and CD8 + T Cell Exhaustion

This review focuses on two core immunosuppressive mechanisms within the tumor immune microenvironment (TIME): the polarization of tumor-associated macrophages (TAMs) towards an M2 phenotype and the functional exhaustion of CD8⁺ T cells. We systematically elucidate the multi-dimensional strategies by which Traditional Chinese Medicine (TCM) remodels the TIME. The article first dissects the interplay between TAMs and CD8⁺ T cells and their pivotal role in tumor immune escape. It then comprehensively reviews how TCM formulations and active components, through their characteristic multi-target actions, coordinately reverse TAM polarization and T cell exhaustion by modulating key signaling pathways (e.g., STAT, PI3K/Akt), reprogramming cellular metabolism (e.g., glycolysis, oxidative phosphorylation), and reshaping cytokine networks. Particular emphasis is placed on metabolic reprogramming as an upstream "bridging" mechanism that concurrently regulates both processes. Finally, the review explores the synergistic potential of combining TCM with immune checkpoint inhibitors and analyzes current challenges, including compositional complexity, insufficient mechanistic depth, and a paucity of high-quality clinical evidence. This work aims to provide a theoretical foundation and forward-looking perspective for developing novel TCM-based strategies in cancer immunotherapy.