Targeting immune checkpoints: New opportunity for mesothelioma treatment?

Cancer Treat Rev. 2015 Dec;41(10):914-24. doi: 10.1016/j.ctrv.2015.09.006. Epub 2015 Sep 28.

Abstract

Malignant pleural mesothelioma is an aggressive cancer linked to asbestos exposure in most patients. Due to the long latency between exposure and presentation, incidence is expected to further increase in the next decade, despite the ban on asbestos import which occurred at the end of last century in industrialized countries. Platinum-based palliative chemotherapy is the only treatment with proven benefit on outcome, resulting in selected patients in a median overall survival of about 1 year. Therefore, there is room for therapeutic improvement using a new strategy to prolong survival. Dealing with cancer cell induced immunosuppression is a promising approach. Reactivating immune responses that are silenced by immune checkpoints recently gained a lot of interest. Checkpoint blockade has already shown promising preclinical and clinical results in several cancer types and is currently also being investigated in mesothelioma. Here, we discuss the expression patterns and mechanisms of action of CTLA-4 and PD-1 as the two most studied and of TIM-3 and LAG-3 as two interesting upcoming immune checkpoints. Furthermore, we review the clinical results of molecules blocking these immune checkpoints and point out their future opportunities with a special focus on mesothelioma.

Keywords: Cytotoxic T-lymphocyte antigen-4; Immune checkpoint; Immunotherapy; Mesothelioma; Programmed death-1.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antigens, CD / immunology
  • Antineoplastic Agents / therapeutic use*
  • B7-H1 Antigen / antagonists & inhibitors
  • B7-H1 Antigen / immunology
  • CTLA-4 Antigen / antagonists & inhibitors*
  • CTLA-4 Antigen / immunology
  • Hepatitis A Virus Cellular Receptor 2
  • Humans
  • Immunologic Factors / therapeutic use*
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / immunology
  • Membrane Proteins / antagonists & inhibitors
  • Membrane Proteins / immunology
  • Mesothelioma / drug therapy*
  • Mesothelioma / immunology
  • Mesothelioma, Malignant
  • Pleural Neoplasms / drug therapy*
  • Pleural Neoplasms / immunology
  • Programmed Cell Death 1 Ligand 2 Protein / antagonists & inhibitors
  • Programmed Cell Death 1 Ligand 2 Protein / immunology
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors*
  • Programmed Cell Death 1 Receptor / immunology

Substances

  • Antigens, CD
  • Antineoplastic Agents
  • B7-H1 Antigen
  • CD223 antigen
  • CTLA-4 Antigen
  • HAVCR2 protein, human
  • Hepatitis A Virus Cellular Receptor 2
  • Immunologic Factors
  • Membrane Proteins
  • Programmed Cell Death 1 Ligand 2 Protein
  • Programmed Cell Death 1 Receptor