Immune Check Point Inhibitors in Primary Cutaneous T-Cell Lymphomas: Biologic Rationale, Clinical Results and Future Perspectives

Abstract

Primary cutaneous T-cell lymphomas (PCTCL) are the most common types of cutaneous lymphomas, with Mycosis fungoides as the most frequent subtype. Besides early stages which usually have a good prognosis, advanced stages remain a great therapeutic challenge with low survival rates. To date, none of the currently available therapeutic options have significantly improved the outcomes of advanced cutaneous lymphomas. Recent studies have demonstrated that immune-checkpoint molecules, such as PD-1 and CTLA-4, play part in the proliferation pathways of neoplastic T-cells, as well as in other tumors. Hence, the potential role of immune-checkpoint-inhibitors in treating cutaneous lymphomas has been investigated in the last years. Herein, we outline the current knowledge regarding the role of immune-checkpoint molecules in PCTCL, their signaling pathways, microenvironment and therapeutic inhibition rationale. Moreover, we review the published data on immunotherapies in PCTCL and summarize the currently ongoing clinical trials in this field.

Keywords: Cutaneous T-cell lymphomas; Mycosis fungoides; Sézary syndrome; immune-checkpoint-inhibitors; immunotherapy; nivolumab; pembrolizumab.