Opportunities and challenges in combining immunotherapy and radiotherapy in esophageal cancer

J Cancer Res Clin Oncol. 2023 Dec;149(20):18253-18270. doi: 10.1007/s00432-023-05499-z. Epub 2023 Nov 20.

Abstract

Background: Immunotherapy has shown promise in the treatment of esophageal cancer, but using it alone only benefits a small number of patients. Most patients either do not have a significant response or develop secondary drug resistance. The combination of radiotherapy and immunotherapy appears to be a promising approach to treating esophageal cancer.

Purpose: We reviewed milestone clinical trials of radiotherapy combined with immunotherapy for esophageal cancer. We then discussed potential biomarkers for radiotherapy combined with immunotherapy, including programmed cell death-ligand 1 (PD-L1) status, tumor mutation burden (TMB), tumor-infiltrating lymphocytes, ct-DNA, imaging biomarkers, and clinical factors. Furthermore, we emphasize the key mechanisms of radiation therapy-induced immune stimulation and immune suppression in order to propose strategies for overcoming immune resistance in radiation therapy (RT). Lastly, we discussed the emerging role of low-dose radiotherapy (LDRT) , which has become a promising approach to overcome the limitations of high-dose radiotherapy.

Conclusion: Radiotherapy can be considered a triggering factor for systemic anti-tumor immune response and, with the assistance of immunotherapy, can serve as a systemic treatment option and potentially become the standard treatment for cancer patients.

Keywords: Esophageal cancer; Immune checkpoint inhibitors; Immunotherapy; Low-dose radiotherapy; Radiotherapy; Radiotherapy combined with immunotherapy.

Publication types

  • Review

MeSH terms

  • B7-H1 Antigen
  • Biomarkers, Tumor
  • Combined Modality Therapy
  • Esophageal Neoplasms* / therapy
  • Humans
  • Immunotherapy* / methods

Substances

  • Biomarkers, Tumor
  • B7-H1 Antigen