Tumor microenvironment and CAR‐T cell immunotherapy in B‐cell lymphoma

Abstract

AbstractChimeric receptor antigen T cell (CAR‐T cell) therapy has demonstrated effectiveness and therapeutic potential in the immunotherapy of hematological malignancies, representing a promising breakthrough in cancer treatment. Despite the efficacy of CAR‐T cell therapy in B‐cell lymphoma, response variability, resistance, and side effects remain persistent challenges. The tumor microenvironment (TME) plays an intricate role in CAR‐T cell therapy of B‐cell lymphoma. The TME is a complex and dynamic environment that includes various cell types, cytokines, and extracellular matrix components, all of which can influence CAR‐T cell function and behavior. This review discusses the design principles of CAR‐T cells, TME in B‐cell lymphoma, and the mechanisms by which TME influences CAR‐T cell function. We discuss emerging strategies aimed at modulating the TME, targeting immunosuppressive cells, overcoming inhibitory signaling, and improving CAR‐T cell infiltration and persistence. Therefore, these processes enhance the efficacy of CAR‐T cell therapy and improve patient outcomes in B‐cell lymphoma. Further research will be needed to investigate the molecular and cellular events that occur post‐infusion, including changes in TME composition, immune cell interactions, cytokine signaling, and potential resistance mechanisms. Understanding these processes will contribute to the development of more effective CAR‐T cell therapies and strategies to mitigate treatment‐related toxicities.