The interplay between immune cells and the tumor microenvironment: from immunosurveillance to immunotherapy

The immune system constitutes a highly coordinated network of cellular and molecular components that protect the host from infection, tissue injury, and malignant transformation. Immune cells, encompassing innate and adaptive lineages, serve as core effectors of this system. Innate immune cells, including macrophages, DCs, and NK cells, initiate rapid, nonspecific responses while shaping subsequent adaptive immunity. Adaptive immune cells, primarily T lymphocytes and B lymphocytes, mediate antigen-specific responses and long-term immunological memory. Within the tumor microenvironment (TME), these populations exhibit context-dependent functions, with cytotoxic subsets exerting tumor control and regulatory subsets facilitating immune evasion. TAMs, Tregs, and MDSCs exemplify immunosuppressive mechanisms, whereas cytotoxic CD8⁺ T cells, NK cells, and DCs drive anti-tumor immunity. Cancer immunotherapy has harnessed these mechanisms, employing immune checkpoint inhibitors targeting PD-1, PD-L1, or CTLA-4, adoptive cell therapies such as chimeric antigen receptor T cell (CAR-T) therapy and tumor-infiltrating lymphocyte (TIL) therapy, as well as therapeutic cancer vaccines. Advances in single-cell RNA sequencing and spatial transcriptomics have revealed extensive cellular heterogeneity and spatial organization within the TME, uncovering mechanisms of immune suppression and therapeutic resistance. Integrating these high-dimensional approaches with rationally designed combination therapies provides a framework for personalized immunotherapy. This review presents a comprehensive overview of immune cell roles in tumor progression, immune evasion, and therapeutic intervention, highlighting strategies to exploit the immune landscape for durable clinical benefit.