Immunocytes in the tumor microenvironment: recent updates and interconnections Affiliations Jiyao Yu

Jiyao Yu ^1,2 Li Fu ^3,4 瑞 巫 ^4,5 Linyi Che ^4,6 Guodong Liu ⁴ Xisong Liang ^2* Zhiwei Xia ^7*

• ¹ Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, England, United Kingdom
• ² Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
• ³ Department of Gastroenterology, Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
• ⁴ Department of Neurosurgery, Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
• ⁵ Department of Neurosurgery, Jiangyou People's Hospital, mianyang, China
• ⁶ Department of Neurology, First Affiliated Hospital of Chongqing Medical University, Chongqing, China
• ⁷ Department of Neurology, Hunan Aerospace Hospital, Changsha, Hunan Province, China

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, immunepromoting 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.