Gastroesophageal cancer: Navigating the immune and genetic terrain to improve clinical outcomes

Cancer Treat Rev. 2020 Mar:84:101950. doi: 10.1016/j.ctrv.2019.101950. Epub 2019 Dec 10.

Abstract

Recent advances in our understanding of the molecular biology of gastric and oesophageal cancers have shown that gastroesophageal adenocarcinoma should be considered as one disease spectrum. Clinical management of these cancers is challenging, with poor outcomes in both early and late disease settings. Certain molecular subsets of gastroesophageal adenocarcinoma demonstrate features that suggest immunotherapy could be an effective treatment. Immunogenetic markers, including mismatch repair deficiency, PD-L1 status and tumour infiltrating lymphocytes influence overall prognosis. They may also determine the response to adjuvant and neoadjuvant conventional chemotherapy. Initial results from immunotherapy trials for gastroesophageal cancer have however been mixed, with poor overall responses in the first- and second-line settings. This review aims to discuss how better understanding of these immune and genetic interactions may lead to better selection of patients for conventional and immune based therapies, and therefore improve patient outcomes. We also discuss the challenges in implementing this new understanding in routine practice, and the current limitations of immune based treatments for gastroesophageal cancer.

Keywords: Adjuvant chemotherapy; Gastroesophageal cancer; Immunotherapy; Mismatch repair; PD-L1; Tumour infiltrating lymphocytes.

Publication types

  • Review

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / genetics
  • Adenocarcinoma / immunology
  • Antigens, Neoplasm / immunology
  • Antineoplastic Agents, Immunological / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • B7-H1 Antigen / immunology
  • B7-H1 Antigen / metabolism
  • Chemotherapy, Adjuvant
  • DNA Mismatch Repair / genetics
  • Esophageal Neoplasms / drug therapy*
  • Esophageal Neoplasms / genetics
  • Esophageal Neoplasms / immunology
  • Humans
  • Immunogenetic Phenomena
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Major Histocompatibility Complex / genetics
  • Major Histocompatibility Complex / immunology
  • Microsatellite Instability
  • Neoadjuvant Therapy
  • Patient Selection
  • Stomach Neoplasms / drug therapy*
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / immunology
  • Tumor Escape / immunology
  • Tumor Microenvironment / immunology

Substances

  • Antigens, Neoplasm
  • Antineoplastic Agents, Immunological
  • B7-H1 Antigen