Immunocytes in the tumor microenvironment: recent updates and interconnections

• Published in: Frontiers in immunology Vol. 16; p. 1517959
• Main Authors: Yu, Jiyao, Fu, Li, Wu, Rui, Che, Linyi, Liu, Guodong, Ran, Qinwen, Xia, Zhiwei, Liang, Xisong, Zhao, Guanjian
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 14.04.2025
• Subjects: Animals; cancer immunity; Dendritic Cells - immunology; Dendritic Cells - metabolism; Humans; immune checkpoints; Immunology; immunosuppression; Immunotherapy - methods; Killer Cells, Natural - immunology; Killer Cells, Natural - metabolism; lymphocytes; Macrophages - immunology; Macrophages - metabolism; myeloid cells; Myeloid-Derived Suppressor Cells - immunology; Neoplasms - immunology; Neoplasms - metabolism; Neoplasms - pathology; Neoplasms - therapy; Tumor Microenvironment - immunology; immunosuppression; lymphocytes; myeloid cells; cancer immunity; immune checkpoints
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2025.1517959

The tumor microenvironment (TME) is a complex, dynamic ecosystem where tumor cells interact with diverse immune and stromal cell types. This review provides an overview of the TME’s evolving composition, emphasizing its transition from an early pro-inflammatory, immune-promoting state to a later immunosuppressive milieu characterized by metabolic reprogramming and hypoxia. It highlights the dual roles of key immunocytes—including T lymphocytes, natural killer cells, macrophages, dendritic cells, and myeloid-derived suppressor cells—which can either inhibit or support tumor progression based on their phenotypic polarization and local metabolic conditions. The article further elucidates mechanisms of immune cell plasticity, such as the M1/M2 macrophage switch and the balance between effector T cells and regulatory T cells, underscoring their impact on tumor growth and metastasis. Additionally, emerging therapeutic strategies, including checkpoint inhibitors and chimeric antigen receptor (CAR) T and NK cell therapies, as well as approaches targeting metabolic pathways, are discussed as promising avenues to reinvigorate antitumor immunity. By integrating recent molecular insights and clinical advancements, the review underscores the importance of deciphering the interplay between immunocytes and the TME to develop more effective cancer immunotherapies.