Increased PD-1 expression on CD4+ and CD8+ T cells is involved in immune evasion in gastric cancer
Abstract
BACKGROUND: Co-signaling molecules play an important role in T cells. Programmed death-1 (PD-1) is an immunoinhibitory receptor and its overexpression on T cells appears to be involved in immune evasion in cancer patients. The present study was designed to investigate PD-1 expression on T cells and its relationship with immune evasion in gastric cancer patients. METHODS: PD-1 expression on CD4+ and CD8+ T cells obtained from peripheral blood mononuclear cells (PBMC), normal gastric mucosa, and gastric cancer tissue was evaluated by multicolor flow cytometry. RESULTS: PD-1 expression on CD4+ and CD8+ T cells from gastric cancer patients was significantly higher than that from normal controls. PD-1 expression on CD4+ and CD8+ T cells was related to disease progression. Furthermore, PD-1 expression on CD4+ and CD8+ T cells from gastric cancer tissue was significantly higher than that from normal gastric mucosa and PBMC. PD-1 positive CD4+ and CD8+ T cells produced significantly less IFN-gamma than PD-1 negative CD4+ and CD8+ T cells. CONCLUSIONS: Upregulation of PD-1 on both CD4+ and CD8+ T cells may be, in part, responsible for immune evasion in gastric cancer patients.
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Blocking antibodies targeting PD-1 signaling mainly affect the effector stage of the immune response.
“PD-1-expressing tumor-infiltrating T cells can be disabled by PD-L1 on the surfaces of tumor cells or other infiltrating immune cells, and blocking antibodies targeting PD-1 signaling are therefore thought to mainly affect the effector stage of the immune response (13, 55–57).”
From Anti-PD-1 and Anti-CTLA-4 Therapies in Cancer: Mechanisms of Action, Efficacy, and Limitations (2018) · cites this paper as [57]
PD-L1 on tumor cells or other infiltrating immune cells can disable PD-1-expressing tumor-infiltrating T cells.
“PD-1-expressing tumor-infiltrating T cells can be disabled by PD-L1 on the surfaces of tumor cells or other infiltrating immune cells, and blocking antibodies targeting PD-1 signaling are therefore thought to mainly affect the effector stage of the immune response (13, 55–57).”
From Anti-PD-1 and Anti-CTLA-4 Therapies in Cancer: Mechanisms of Action, Efficacy, and Limitations (2018) · cites this paper as [57]
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- Authors
- Saito, H., Kuroda, H., Matsunaga, T., Osaki, T., & Ikeguchi, M.
- Affiliations
- Tottori University Hospital (JP)
- Corresponding author
- Saito, Hiroaki
- Venue
- Journal of Surgical Oncology
- Publisher
- Wiley
- Published
- 2012-11-05
- Volume
- 107
- Issue
- 5
- Pages
- 517-522
- ISSN
- 0022-4790 (ISSN-L)
- 1096-9098
- OpenAlex
- W1498454097
- Cited by
- 94
- References
- 39
- Citations by year
- 2026: 3 · 2025: 8 · 2024: 4 · 2023: 6 · 2022: 2 · 2021: 7 · 2020: 10 · 2019: 6 · 2018: 11 · 2017: 15 · 2016: 12 · 2015: 6 · 2014: 2 · 2013: 2
- FWCI
- 1.58
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Surgical Oncology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Japan Society for the Promotion of Science (23501285)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- PD-1, PDCD1, gastric cancer, immune evasion, CD4+ T cells, CD8+ T cells, IFN-gamma production, disease progression, tumor-infiltrating lymphocytes
- MeSH terms
- Aged, Female, Flow Cytometry, Humans, Interferon-gamma, Male, Monocytes, Stomach Neoplasms, CD4-Positive T-Lymphocytes, Up-Regulation, Case-Control Studies, CD8-Positive T-Lymphocytes, Lipopolysaccharide Receptors, Programmed Cell Death 1 Receptor
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