Immunotherapy in thymic epithelial tumors: tissue predictive biomarkers for immune checkpoint inhibitors

Abstract

Thymic epithelial tumors (TETs) are rare malignant neoplasms arising in the thymus gland. Nevertheless, TETs, including thymomas (TMs), thymic carcinomas (TCs), and thymic neuroendocrine neoplasms (TNENs), are the most common mediastinal malignancies overall. A multidisciplinary approach is required for the appropriate diagnostic and therapeutic management of TETs. To date, the main therapeutic strategies are largely depended on the stage of the tumor and they include surgery with or without neoadjuvant or adjuvant therapy, represented by platinum-based chemotherapy, radiotherapy or chemoradiotherapy. Immune checkpoint inhibitors (ICIs) are ongoing under evaluation in the advanced or metastatic diseases despite the challenges related to the very low tumor mutation burden (TMB) and the high incidence of immune-related adverse events in TETs. In this regard, predictive impact of tissue biomarkers expression such as programmed cell death ligand-1 (PD-L1), and other emerging biomarkers, as well as their optimal and shared interpretation are currently under evaluation in order to predict response rates to ICIs in TETs.

Keywords: Thymic epithelial tumors; immunotherapy; thymic carcinoma; thymoma.

Figure 1

Programmed cell death ligand-1 (PD-L1) expression on tumor cells of TETs. (A) Histopathological appearance of type B2 TM; (B) diffuse and strong immunohistochemical (IHC) membranous staining (MS) for PD-L1 (clone SP263; Ventana Medical Systems) in ≥ 50% of neoplastic cells in type B2 TM and squamous cell carcinoma of the thymus; (C) squamous cell carcinoma of the thymus (hematoxylin and eosin); (D) squamous cell carcinoma of the thymus. A–D, scale bar = 100 μm; original magnifications ×200. Courtesy of Pathology Unit of Università degli Studi della Campania “L. Vanvitelli”