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Cytotoxic T-lymphocyte-associated protein 4 in gastric cancer: Prognosis and association with PD-L1 expression.

Authors
  • Pereira, Marina Alessandra1
  • de Castria, Tiago Biachi1
  • Ramos, Marcus Fernando Kodama Pertille1
  • Dias, André Roncon1
  • Cardili, Leonardo1
  • de Moraes, Rafael Dyer Rodrigues1
  • Zilberstein, Bruno1
  • Nahas, Sergio Carlos1
  • Ribeiro, Ulysses Jr1
  • de Mello, Evandro Sobroza1
  • 1 Department of Gastroenterology, Department of Pathology, Faculdade de Medicina, Instituto do Cancer do Estado de São Paulo, Hospital das Clinicas HCFMUSP, Universidade de Sao Paulo, Sao Paulo, Brazil. , (Brazil)
Type
Published Article
Journal
Journal of Surgical Oncology
Publisher
Wiley (John Wiley & Sons)
Publication Date
Dec 01, 2021
Volume
124
Issue
7
Pages
1040–1050
Identifiers
DOI: 10.1002/jso.26604
PMID: 34255356
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) is one of the most studied immune checkpoint in gastric cancer (GC). However, the prognostic role of CTLA-4 expression in GC is poorly described. This study aimed to evaluate CTLA-4 expression in GC and its impact on survival, including patients treated with standard platinum-based chemotherapy (CMT), and association with PD-L1 expression. All GC patients who underwent D2-gastrectomy were investigated retrospectively. Tumor samples were examined for CTLA-4 and PD-L1 by immunohistochemistry. Tumor-infiltrating inflammatory cells, including CD4 + and CD8 + , were also examined. Among the 284 GC patients included, 159 (56%) were CTLA-4 positive and the remaining 125 (44%) were classified as negative. CTLA-4 positive GC was associated with increased inflammatory cell infiltration (p < 0.001), high CD8 + T cells (p = 0.016) and PD-L1 expression (p = 0.026). Considering GC referred for treatment, CTLA-4 negative patients who received CMT had a significant improvement in disease-free survival compared to untreated CLTA-4 negative (p = 0.028). In multivariate analysis, GC positive for both CTLA-4 and PD-L1 had a prognostic impact on survival. CTLA-4 positive was associated with PD-L1 expression and a high tumor-infiltrating CD8 + T cells. Accordingly, positivity for both CTLA-4 and PD-L1 was an independent factor associated to better survival in GC patients. © 2021 Wiley Periodicals LLC.

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