Lacking Immunotherapy Biomarkers for Biliary Tract Cancer: A Comprehensive Systematic Literature Review and Meta-Analysis

Cells. 2023 Aug 19;12(16):2098. doi: 10.3390/cells12162098.

Abstract

Background: Immunotherapy has recently been incorporated into the spectrum of biliary tract cancer (BTC) treatment. The identification of predictive response biomarkers is essential in order to identify those patients who may benefit most from this novel treatment option. Here, we propose a systematic literature review and a meta-analysis of PD-1, PD-L1, and other immune-related biomarker expression levels in patients with BTC.

Methods: Prisma guidelines were followed for this systematic review and meta-analysis. Eligible studies were searched on PubMed. Studies published between 2017 and 2022, reporting data on PD-1/PD-L1 expression and other immune-related biomarkers in patients with BTC, were considered eligible.

Results: A total of 61 eligible studies were identified. Despite the great heterogeneity between 39 studies reporting data on PD-L1 expression, we found a mean PD-L1 expression percentage (by choosing the lowest cut-off per study) of 25.6% (95% CI 21.0 to 30.3) in BTCs. The mean expression percentages of PD-L1 were 27.3%, 21.3%, and 27.4% in intrahepatic cholangiocarcinomas (iCCAs-15 studies), perihilar-distal CCAs (p/dCCAs-7 studies), and gallbladder cancer (GBC-5 studies), respectively. Furthermore, 4.6% (95% CI 2.38 to 6.97) and 2.5% (95% CI 1.75 to 3.34) of BTCs could be classified as TMB-H and MSI/MMRd tumors, respectively.

Conclusion: From our analysis, PD-L1 expression was found to occur approximately in 26% of BTC patients, with minimal differences based on anatomical location. TMB-H and MSI molecular phenotypes occurred less frequently. We still lack a reliable biomarker, especially in patients with mismatch-proficient tumors, and we must need to make an effort to conceive new prospective biomarker discovery studies.

Keywords: biliary cancer; immunotherapy; predictive biomarkers.

Publication types

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

MeSH terms

  • B7-H1 Antigen
  • Bile Duct Neoplasms*
  • Bile Ducts, Intrahepatic
  • Biliary Tract Neoplasms* / therapy
  • Biomarkers
  • Humans
  • Immunotherapy
  • Programmed Cell Death 1 Receptor

Substances

  • B7-H1 Antigen
  • Programmed Cell Death 1 Receptor
  • Biomarkers

Grants and funding

Angela Lamarca received funding from the Spanish Society of Medical Oncology (SEOM) Fellowship Program (Return Fellowship) and European Union’s Horizon 2020 Research and Innovation Program [grant number 825510, ESCALON]. Rocio IR Macias received funding from the Instituto de Salud Carlos III, Spain (PI20/00189), co-financed by the European Regional Development Fund.