Programmed cell death protein-1/programmed cell death ligand-1 pathway inhibition and predictive biomarkers: Understanding transforming growth factor-beta role

Mariacarmela Santarpia, María González-Cao, Santiago Viteri, Niki Karachaliou, Giuseppe Altavilla, Rafael Rosell

Research output: Contribution to journalArticle

Abstract

A deeper understanding of the key role of the immune system in regulating tumor growth and progression has led to the development of a number of immunotherapies, including cancer vaccines and immune checkpoint inhibitors. Immune checkpoint inhibitors target molecular pathways involved in immunosuppression, such as cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) and programmed cell death protein-1 (PD-1)/programmed cell death ligand-1 (PD-L1) pathway, with the goal to enhance the host's own immune anticancer response. In phase I-III trials, anti-PD-1/PD-L1 antibodies have demonstrated to be effective treatment strategies by inducing significant durable tumor responses, with manageable toxicities, in patients with various malignancies, including those traditionally considered nonimmunogenic, such as non-small cell lung cancer (NSCLC). Identification of predictive biomarkers to select patients for immune therapies is currently being investigated to improve their therapeutic efficacy. Transforming growth factor-β (TGF-β), a pleiotropic cytokine with immunosuppressive effects on multiple cell types of the innate and adaptive immune system, has emerged as one of the potential key factors modulating response to immune checkpoint inhibitors. However, due to the complexity of the anti-cancer immune response, the predictive value of many other factors related to cancer cells or tumor microenvironment needs to be further explored.

Original languageEnglish
Pages (from-to)728-742
Number of pages15
JournalTranslational Lung Cancer Research
Volume4
Issue number6
DOIs
Publication statusPublished - 2015

Keywords

  • (TGF-β)
  • Immunotherapy
  • Non-small cell lung cancer (NSCLC)
  • Programmed cell death protein-1 (PD-1)/programmed cell death ligand-1 (PD-L1)
  • Transforming growth factor-β

ASJC Scopus subject areas

  • Oncology

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