The Tumor Microenvironment as a Therapeutic Target in Cutaneous T Cell Lymphoma.

Simple Summary: Cutaneous T cell lymphomas (CTCLs) are a group of rare lymphoproliferative malignancies manifesting in the skin. Cutaneous T cell lymphomas are an incurable, disfiguring, and life-threatening disease. Emerging studies have implicated the surrounding cells of malignant T cells (tumor microenvironment) in the disease evolution. This has revealed that targeting the tumor microenvironment has therapeutic potential in cutaneous T cell lymphomas. This review provides a detailed insight into the contribution of the tumor microenvironment in cutaneous T cell lymphomas and the targeting strategies. Cutaneous T cell lymphomas (CTCLs) are a heterogeneous group of non-Hodgkin lymphomas, with mycosis fungoides and Sézary syndrome being the two common subtypes. Despite the substantial improvement in early-stage diagnosis and treatments, some patients still progress to the advanced stage with an elusive underpinning mechanism. While this unsubstantiated disease mechanism coupled with diverse clinical outcomes poses challenges in disease management, emerging evidence has implicated the tumor microenvironment in the disease process, thus revealing a promising therapeutic potential of targeting the tumor microenvironment. Notably, malignant T cells can shape their microenvironment to dampen antitumor immunity, leading to Th2-dominated responses that promote tumor progression. This is largely orchestrated by alterations in cytokines expression patterns, genetic dysregulations, inhibitory effects of immune checkpoint molecules, and immunosuppressive cells. Herein, the recent insights into the determining factors in the CTCL tumor microenvironment that support their progression have been highlighted. Also, recent advances in strategies to target the CTCL tumor micromovement with the rationale of improving treatment efficacy have been discussed. [ABSTRACT FROM AUTHOR]