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PD-1/PD-L1 Pathway and Its Blockade in Patients with Classic Hodgkin Lymphoma and Non-Hodgkin Large-Cell Lymphomas

  • Molecular Testing and Diagnostics (J Khoury, Section Editor)
  • Published:
Current Hematologic Malignancy Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

Programmed cell death protein-1 (PD-1) is currently the most extensively studied inhibitory checkpoint molecule. Many malignant neoplasms express the PD-1 ligands, PD-L1, and/or PD-L2, which bind to PD-1 on T cells and induce T cell “exhaustion.” By doing so, the malignant cells escape from an antitumor immune response (immune evasion). Blockade of the PD-1/PD-L1 pathway releases T cells from the inhibitory effects exerted by tumor cells and restores a T cell-mediated antitumor immune response. Here, we focus on understanding the immune biology of the PD-1/PD-L1 pathway in large-cell lymphomas, including classic Hodgkin lymphoma (CHL), diffuse large B cell lymphoma (DLBCL), and anaplastic large-cell lymphoma (ALCL), and the current status of PD-1 blockade immunotherapy in treating patients with these lymphomas.

Recent Findings

PD-1/PD-L1 pathway and PD-1 inhibitors have been widely tested in patients with a variety of lymphomas. Nivolumab and pembrolizumab have been approved by the U.S. Food and Drug Administration for treating patients with some types of relapsed or refractory (R/R) lymphomas. The highest response rate has been achieved in patients with CHL, due to a high frequency of genetic alterations of 9p24.1 and high expression of PD-1 ligands. The frequency of alterations of chromosome 9p24.1 and expression of PD-L1/PD-L1 in DLBCL (except some specific subtypes) is low; therefore, it is not recommended to treat unselected DLBCL patients with PD-1 inhibitors. Studies have shown a high frequency of PD-L1 expression in ALCL, especially in anaplastic lymphoma kinase (ALK)+ type. Several cases reports have described a dramatic and durable response to PD-1 blockade in patients with R/R ALCL, suggesting that patients with R/R ALCL may be potential candidates for PD-1 blockade immunotherapy.

Summary

Understanding the immune biology of lymphoid neoplasms has helped us identify the specific lymphoma types that are vulnerable to PD-1 inhibitors, such as CHL, and specific subtypes of DLBCL. However, our knowledge of many other lymphomas, including ALCL, in this area is still very limited and the future of PD-1 inhibitors in treating those lymphomas remains unclear.

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  1. Department of Hematopathology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Unit 0072, Houston, TX, 77030, USA

    Wei Xie, L. Jeffrey Medeiros, Shaoying Li, C. Cameron Yin, Joseph D. Khoury & Jie Xu

  2. Department of Pathology & Immunology, Baylor College of Medicine, Houston, TX, USA

    Wei Xie

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Xie, W., Medeiros, L.J., Li, S. et al. PD-1/PD-L1 Pathway and Its Blockade in Patients with Classic Hodgkin Lymphoma and Non-Hodgkin Large-Cell Lymphomas. Curr Hematol Malig Rep 15, 372–381 (2020). https://doi.org/10.1007/s11899-020-00589-y

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