The Immunopathogenesis and Immunotherapy of Cutaneous T Cell Lymphoma: Part II, Current and Future Approaches

In the past few decades, immunotherapy has emerged as an effective therapeutic option for patients with cutaneous T cell lymphoma (CTCL). CTCL is characterized by progressive impairment of multiple arms of the immune system. Immunotherapy targets these deficits to stimulate a more robust anti-tumor response, thereby both clearing the malignant T cells and repairing the immune dysfunction. By potentiating rather than suppressing the immune system, immunotherapy can result in longer treatment responses than alternatives such as chemotherapy. In recent years, advances in our understanding of the pathogenesis of CTCL have led to the development of several new agents with promising efficacy profiles. In part II of this review, we describe the current immunotherapeutic options for treatment of CTCL, with a focus on how they interact with the immune system and their treatment outcomes in case studies and clinical trials. In particular, we will discuss established CTCL immunotherapies such as interferons, photopheresis, and retinoids; emerging therapies such as interleukin-12 and TLR-agonists; and new approaches to targeting tumor antigens and checkpoint molecules such as mogamulizumab, anti-PD1, anti-CD47, and CAR-T therapy. We also describe the principles of multimodality immunotherapy and the use of TSEBT in such regimens.