Immune cells and checkpoints in pancreatic adenocarcinoma: Association with clinical and pathological characteristics.

Autor: Cysneiros MAPC; Diagnostic and Therapeutic Support Division of Clinical Hospital, Federal University of Goias, Goiania, Brazil., Cirqueira MB; Diagnostic and Therapeutic Support Division of Clinical Hospital, Federal University of Goias, Goiania, Brazil., Barbosa LF; Pathology Department, Federal University of São Paulo, São Paulo, Brazil., Chaves de Oliveira Ê; Surgery Department of Medicine College, Federal University of Goias, Goiania, Brazil., Morais LK; Surgery Department of Medicine College, Federal University of Goias, Goiania, Brazil., Wastowski IJ; Biological Sciences and Health Institute, State University of Goias, Goiania, Brazil., Floriano VG; Clinics Department of Medicine College, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2024 Jul 02; Vol. 19 (7), pp. e0305648. Date of Electronic Publication: 2024 Jul 02 (Print Publication: 2024).
DOI: 10.1371/journal.pone.0305648
Abstrakt: Introduction: Pancreatic adenocarcinoma is an extremely aggressive neoplasm, with many challenges to be overcome in order to achieve a truly effective treatment. It is characterized by a mostly immunosuppressed environment, with dysfunctional immune cells and active immunoinhibitory pathways that favor tumor evasion and progression. Thus, the study and understanding of the tumor microenvironment and the various cells subtypes and their functional capacities are essential to achieve more effective treatments, especially with the use of new immunotherapeutics.
Methods: Seventy cases of pancreatic adenocarcinoma divided into two groups 43 with resectable disease and 27 with unresectable disease were analyzed using immunohistochemical methods regarding the expression of programmed cell death ligand 1 (PD-L1), programmed cell death ligand 2 (PD-L2), and human leukocyte antigen G (HLA-G) molecules as well as the populations of CD4+ and CD8+ T lymphocytes, regulatory T cells (Tregs), and M2 macrophages (MM2). Several statistical tests, including multivariate analyses, were performed to examine how those immune cells and immunoinhibitory molecules impact the evolution and prognosis of pancreatic adenocarcinoma.
Results: CD8+ T lymphocytes and M2 macrophages predominated in the group operated on, and PD-L2 expression predominated in the unresectable group. PD-L2 was associated with T stage, lymph node metastasis, and clinical staging, while in survival analysis, PD-L2 and HLA-G were associated with a shorter survival. In the inoperable cases, Tregs cells, MM2, PD-L1, PD-L2, and HLA-G were positively correlated.
Conclusions: PD-L2 and HLA-G expression correlated with worse survival in the cases studied. Tumor microenvironment was characterized by a tolerant and immunosuppressed pattern, mainly in unresectable lesions, where a broad positive influence was observed between immunoinhibitory cells and immune checkpoint proteins expressed by tumor cells.
Competing Interests: The authors have declared that no competing interests exist.
(Copyright: © 2024 Cysneiros et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
Databáze: MEDLINE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje