Understanding the landscape of immunotherapy in thymic epithelial tumors

Abstract Thymic epithelial tumors (TETs) are a rare group of malignancies arising from the thymus. Surgery remains the foundation of treatment for patients with early‐stage disease. Limited treatment options are available for the treatment of unresectable, metastatic, or recurrent TETs and are associated with modest clinical efficacy. The emergence of immunotherapies in the treatment of solid tumors has generated significant interest in understanding their role in TET treatment. However, the high rates of comorbid paraneoplastic autoimmune disorders, particularly in thymoma, have tempered expectations regarding the role of immune‐based therapies. Clinical studies of immune checkpoint blockade (ICB) in thymoma and thymic carcinoma have revealed higher frequencies of immune‐related adverse events (IRAEs) and limited efficacy. Despite these setbacks, the growing understanding of the thymic tumor microenvironment and systemic immune system has advanced the understanding of these diseases and provided opportunities for novel immunotherapy modalities. Ongoing studies are evaluating numerous immune‐based treatments in TETs with the goal of improving clinical efficacy and mitigating IRAE risk. This review will provide insight into the current understanding of the thymic immune microenvironment, outcomes of previous ICB studies, and review treatments currently being explored for the management of TET.