Checkpoint blockade-based immunotherapy in the context of tumor microenvironment: Opportunities and challenges

Cancer Med. 2018 Sep;7(9):4517-4529. doi: 10.1002/cam4.1722. Epub 2018 Aug 7.

Abstract

A dynamic and mutualistic interaction between tumor cells and tumor microenvironment (TME) promotes the progression and metastasis of solid tumors. Cancer immunotherapy is becoming a major treatment paradigm for a variety of cancers. Although immunotherapy, especially the use of immune checkpoint inhibitors, has achieved clinical success, only a minority of patients exhibits durable responses. Clinical studies directed at identifying appropriate biomarkers and immune profiles that can be used to predict immunotherapy responses are presently being conducted. Combining treatment strategies tailored to cancer-immune interactions are designed to increase the rate of durable clinical response in patients. It is essential to establish a reasonable tumor classification strategy according to TME to improve cancer immunotherapy. In the current review, a modified classification of TME is proposed, and optimization of TME classification is needed through detailed and integrated molecular characterization of large patient cohorts in the future.

Keywords: biomarkers; checkpoint inhibitors; combination therapy; immunotherapy; tumor microenvironment.

Publication types

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

MeSH terms

  • Antineoplastic Agents, Immunological / pharmacology
  • Antineoplastic Agents, Immunological / therapeutic use*
  • Biomarkers, Tumor*
  • Combined Modality Therapy
  • Humans
  • Immunomodulation / drug effects*
  • Immunotherapy*
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Lymphocytes, Tumor-Infiltrating / metabolism
  • Molecular Targeted Therapy
  • Neoplasms / drug therapy*
  • Neoplasms / immunology*
  • Neoplasms / pathology
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism
  • Treatment Outcome
  • Tumor Microenvironment / drug effects*
  • Tumor Microenvironment / immunology*

Substances

  • Antineoplastic Agents, Immunological
  • Biomarkers, Tumor