Higher prevalence of LAP+ (Latency TGFβ-Associated Peptide) T cells at the tissue level in patients with early gastric cancer

Cell Immunol. 2022 Dec:382:104635. doi: 10.1016/j.cellimm.2022.104635. Epub 2022 Oct 28.

Abstract

The presence of cells with regulatory functions in patients with cancer is one of the mechanisms whereby the immune system cannot confront tumor growth. We sought to determine the prevalence of immunoregulatory T-cell subpopulations, expressing the latency TGFβ-associated peptide (LAP), in patients with gastric adenocarcinoma. T cells were enriched from blood or gastric tissue (tumoral, TT or tumor-free, TF) samples from 22 patients, 6 with early (EGC) and 16 with advanced gastric cancer (AGC). CD4, CD8, LAP, FoxP3 and IFN-γ were measured by cytometry. CD8 + LAP + cells were increased at tumoral sites, especially in early stages of the disease, as compared to tumor-free explants (EGC 5.28 % [4.67-6.64]*; AGC 2.90 % [1.37-4.44]; TF 3.14 % [2.33-4.16]; *p < 0.05 vs TF). Likewise, the LAP+/CD8 + LAP- ratio is increased in gastric samples from patients with early disease (EGC 0.38 [0.30-0.45]*, AGC 0.12 [0.07-0.14]; TF 0.12 [0.09-0.31]; *p < 0.05 vs AGC).Disease progression is accompanied by decreased LAP membrane expression and, probably, increased LAP secretion, therefore limiting the response to the tumor.

Keywords: FoxP3; Gastric adenocarcinoma; LAP; TGFβ; Treg.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Forkhead Transcription Factors / metabolism
  • Humans
  • Peptides / metabolism
  • Prevalence
  • Stomach Neoplasms* / pathology
  • T-Lymphocytes, Regulatory
  • Transforming Growth Factor beta* / metabolism

Substances

  • Forkhead Transcription Factors
  • Peptides
  • Transforming Growth Factor beta