Unlocking T‐Cell Plasticity in the Tumor Microenvironment: Implications for Cancer Progression and Therapeutic Strategies

ABSTRACT The tumor microenvironment (TME) is a complex and dynamic ecosystem crucial for cancer development and progression. Within this intricate milieu, T‐cells constitute a heterogeneous population and serve as a cornerstone of antitumor immunity. Notably, T‐cells can rapidly transition across a wide spectrum of phenotypic and functional states within the disrupted TME. Despite the crucial role of T‐cells in cancer immunity, a comprehensive understanding of their plasticity within the TME remains limited. In this review, we delve into the functional plasticity and spatial distribution of T‐cells in response to diverse microenvironmental conditions. Additionally, we review the plasticity of T‐cell functional states during conventional therapies, highlighting their potential to enhance or limit therapeutic outcomes. Finally, we propose innovative therapeutic approaches that leverage T‐cell plasticity to enhance clinical efficacy by regulating the immune response within the TME. By providing insights into the dynamics of T‐cell behavior, this review highlights the promising potential of targeting T‐cell plasticity as an immuno‐sensitizer to refine therapeutic strategies and overcome current challenges in cancer treatment.