The Bidirectional Interplay between T Cell-Based Immunotherapies and the Tumor Microenvironment

T cell-based therapies, including tumor-infiltrating lymphocyte therapy, T-cell receptor-engineered T cells, and chimeric antigen receptor T cells, are powerful therapeutic approaches for cancer treatment. Whereas these therapies are primarily known for their direct cytotoxic effects on cancer cells, accumulating evidence indicates that they also influence the tumor microenvironment (TME) by altering the cytokine milieu and recruiting additional effector populations to help orchestrate the antitumor immune response. Conversely, the TME itself can modulate the behavior of these therapies within the host by either supporting or inhibiting their activity. In this review, we provide an overview of clinical and preclinical data on the bidirectional influences between T-cell therapies and the TME. Unraveling the interactions between T cell-based therapies and the TME is critical for a better understanding of their mechanisms of action, resistance, and toxicity, with the goal of optimizing efficacy and safety.