PD-1/PD-L1 Blockade Therapy for Tumors with Downregulated MHC Class I Expression.

Michal Šmahel

doi:10.3390/ijms18061331

Abstract

The therapy of different advanced-stage malignancies with monoclonal antibodies blocking programmed cell death protein 1 (PD-1)/PD-1 ligand 1 (PD-L1) signaling has had an impressive long-lasting effect in a portion of patients, but in most cases, this therapy was not successful, or a secondary resistance developed. To enhance its efficacy in treated patients, predictive biomarkers are searched for and various combination treatments are intensively investigated. As the downregulation of major histocompatibility complex (MHC) class I molecules is one of the most frequent mechanisms of tumor escape from the host’s immunity, it should be considered in PD-1/PD-L1 checkpoint inhibition. The potential for the use of a PD-1/PD-L1 blockade in the treatment of tumors with aberrant MHC class I expression is discussed, and some strategies of combination therapy are suggested.

Highlights

The blockade of inhibitory immune checkpoints with monoclonal antibodies contributed to the revival of interest and belief in cancer immunotherapy
After pioneering studies with a cytotoxic T-lymphocyte associated antigen 4 (CTLA-4; cluster of differentiation (CD) 152) blockade that resulted in the Food and Drug Administration (FDA)’s approval of ipilimumab for the treatment of advanced melanoma in 2011, programmed cell death protein 1 (PD-1; CD279)/PD-1 ligand 1 (PD-L1) signaling is in the focus of the current research on, and the development of, anti-tumor therapy in this field
This is because the blocking of PD-1 or PD-L1 molecules exhibited higher efficacy and lower toxicity for several types of human cancers, including melanoma, non-small cell lung cancer (NSCLC), and renal cell cancer (RCC)

Summary

Introduction

The blockade of inhibitory immune checkpoints with monoclonal antibodies contributed to the revival of interest and belief in cancer immunotherapy. After pioneering studies with a cytotoxic T-lymphocyte associated antigen 4 (CTLA-4; cluster of differentiation (CD) 152) blockade that resulted in the Food and Drug Administration (FDA)’s approval of ipilimumab for the treatment of advanced melanoma in 2011, programmed cell death protein 1 (PD-1; CD279)/PD-1 ligand 1 (PD-L1) signaling is in the focus of the current research on, and the development of, anti-tumor therapy in this field. This is because the blocking of PD-1 or PD-L1 molecules exhibited higher efficacy and lower toxicity for several types of human cancers, including melanoma, non-small cell lung cancer (NSCLC), and renal cell cancer (RCC). Sci. 2017, 18, 1331 cytokines contributing to the differentiation of effector T cells; and (iii) the maintenance of T-cell anergy in peripheral tissues

Tumor Escape by MHC-I Downregulation

Findings

Future Perspectives