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.

Keywords

cancer therapy / spatial architecture / T-cell plasticity / tumor microenvironment

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