Evaluation of soluble co-inhibitors and co-stimulators levels of the immune response in gastric cancer

J Surg Oncol. 2024 Sep;130(4):757-768. doi: 10.1002/jso.27747. Epub 2024 Jun 30.

Abstract

Background: Co-inhibitor and co-stimulator mediators trigger actions that result in immunological homeostasis and are being evaluated as potential therapeutic targets in gastric cancer (GC).

Objective: To evaluate the soluble levels of sPD-1, sPD-L1, sPD-L2, sTIM-3, sGal9, sGITR, and sGITRL in GC patients.

Methods: The cross-sectional study was carried out at the Hospital de Cancer de Pernambuco, Brazil between 2017 and 2018. A total of 74 GC patients and 30 healthy controls were included.

Results: Low levels of sPD1 (p = 0.0179), sPDL2 (p = 0.0003), and sGal9 (p < 0.0001), and higher levels of sPDL1 (p = 0.004), sTIM-3 (p = 0.0072), sGITR (p = 0.0179), and sGITRL (p = 0.0055) compared to the control group. High sPD-1, sTIM-3, and sGal9 levels in stage IV compared I/II and III (p < 0.05). High sPDL1, sGal9, and sGITRL levels in esophagogastric junction compared to body and Pylorus/Antrum groups (p < 0.05). No significant differences were observed in sPD1, sPDL1, sPDL2, sTIM3, sGal9, sGITR, and sGITRL levels between the intestinal, diffuse, and mixed GC groups. Low sGITR levels in GC patients who died within the first 24 months compared to the who survived (p = 0.0332).

Conclusions: There is an association of sPD1, sTIM-3, and sGal9 with disease progression and sGITR with death, these mediators may be potential prognostic biomarkers in GC.

Keywords: biomarkers; co‐inhibitors; co‐stimulators; gastric cancer; immunology; solid tumors.

MeSH terms

  • Adult
  • Aged
  • B7-H1 Antigen
  • Biomarkers, Tumor* / blood
  • Biomarkers, Tumor* / metabolism
  • Case-Control Studies
  • Cross-Sectional Studies
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Middle Aged
  • Prognosis
  • Stomach Neoplasms* / immunology
  • Stomach Neoplasms* / mortality
  • Stomach Neoplasms* / pathology

Substances

  • Biomarkers, Tumor
  • B7-H1 Antigen