Immunochemotherapy benefits in gastric cancer patients stratified by programmed death-1 ligand-1

J Surg Res. 2017 May 1:211:30-38. doi: 10.1016/j.jss.2016.11.058. Epub 2016 Dec 11.

Abstract

Background: Effectiveness of protein-bound polysaccharide K (PSK) during adjuvant chemotherapy in gastric cancer patients expressing programmed death-1 ligand 1 (PD-L1) has not been investigated. Investigating this might help in triaging candidates eligible to immunochemotherapy.

Materials and methods: In total, 918 patients with stages II and III gastric cancer, undergoing curative gastrectomy, and receiving adjuvant chemotherapy were enrolled in a prospective database, and the patients were retrospectively reviewed. We classified those patients into four cohorts stratified by PD-L1 expression and PSK administration, namely PD-L1, PSK (-,+); PD-L1, PSK (-,-); PD-L1, PSK (+,+); and PD-L1, PSK (+,-). In addition, another independent cohort of 20 patients undergoing radical gastrectomy was prospectively recruited to check their immunological cells of sera before and 2 mo after PSK administration.

Results: PSK treatment was an independent prognostic factor for patient's overall survival (P = 0.020), whereas PD-L1 expression per se was not. Administration of PSK prolonged patient survival in stages IIIA and IIIB (P = 0.031) but not in stage II or stage IIIC. Patients with negative expression of PD-L1, treated with PSK had longer survival than those not treated with PSK (P = 0.033). PSK did not affect the survival of patients with positive expression of PD-L1, (P = 0.421). The percentages of natural killer and natural killer T (NKT) cells, but not Th1, Th17, Treg, or IFN-γ+/CD8+ T cells, were significantly increased in PD-L1 (-) patients treated with PSK. However, these findings were not evident in PD-L1 (+) patients.

Conclusions: PSK treatment preferentially confers a survival gain for patients with stage IIIA/IIIB gastric cancer, especially in the PD-L1 (-) subpopulation.

Keywords: Gastric cancer; Natural killer cell; PD-L1; PSK; Prognosis.

Publication types

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

MeSH terms

  • Adjuvants, Immunologic / therapeutic use*
  • Adult
  • Aged
  • Antineoplastic Agents / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • B7-H1 Antigen / metabolism*
  • Biomarkers, Tumor / metabolism*
  • Chemotherapy, Adjuvant
  • Female
  • Fluorouracil / therapeutic use
  • Follow-Up Studies
  • Gastrectomy*
  • Humans
  • Male
  • Middle Aged
  • Prospective Studies
  • Proteoglycans / therapeutic use*
  • Retrospective Studies
  • Stomach Neoplasms / drug therapy*
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / mortality
  • Stomach Neoplasms / surgery
  • Treatment Outcome

Substances

  • Adjuvants, Immunologic
  • Antineoplastic Agents
  • B7-H1 Antigen
  • Biomarkers, Tumor
  • CD274 protein, human
  • Proteoglycans
  • polysaccharide-K
  • Fluorouracil