Tumour microenvironment influences response to treatment in oesophageal adenocarcinoma

Front Immunol. 2023 Dec 13:14:1330635. doi: 10.3389/fimmu.2023.1330635. eCollection 2023.

Abstract

The poor treatment response of oesophageal adenocarcinoma (OAC) leads to low survival rates. Its increasing incidence makes finding more effective treatment a priority. Recent treatment improvements can be attributed to the inclusion of the tumour microenvironment (TME) and immune infiltrates in treatment decisions. OAC TME is largely immunosuppressed and reflects treatment resistance as patients with inflamed TME have better outcomes. Priming the tumour with the appropriate neoadjuvant chemoradiotherapy treatment could lead to higher immune infiltrations and higher expression of immune checkpoints, such as PD-1/PDL-1, CTLA4 or emerging new targets: LAG-3, TIM-3, TIGIT or ICOS. Multiple trials support the addition of immune checkpoint inhibitors to the current standard of care. However, results vary, supporting the need for better response biomarkers based on TME composition. This review explores what is known about OAC TME, the clinical significance of the various cell populations infiltrating it and the emerging therapeutical combination with a focus on immune checkpoints inhibitors.

Keywords: immune checkpoints; immune infiltrate; immunotherapy; oesophageal adenocarcinoma; treatment response; tumour microenvironment.

Publication types

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

MeSH terms

  • Adenocarcinoma* / metabolism
  • Biomarkers
  • Esophageal Neoplasms* / drug therapy
  • Esophageal Neoplasms* / metabolism
  • Humans
  • Tumor Microenvironment

Substances

  • Biomarkers

Supplementary concepts

  • Adenocarcinoma Of Esophagus

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. JL is supported by the UQ Philip Walker Surgery Research Scholarship. SB received funding through the 2021 Priority-driven Collaborative Cancer Research Scheme and funded by Cure Cancer with the support of Cancer Australia (2010313). SB and AB received further funding from the Metro South Health Research Support Scheme (RSS_2022_039).