Abstract
Purpose
Defining the phenotypic characteristics of CD8+ T cell subsets in gastric cancer (GC) can help remodel the immune microenvironment of the tumor, thereby improving patient prognosis. CD226 has recently been shown to regulate the activity of CD8+ T cell in several malignancies. However, the clinical relevance of CD226+CD8+ T cells in GC remains unclear.
Methods
Fudan University Shanghai Cancer Center (FUSCC) cohort (n = 316), The Cancer Genome Atlas (TCGA) cohort (n = 407), KUGH/KUCM cohort (n = 202), and Asian Cancer Research Group (ACRG) cohort (n = 300) were included in prognosis and response to adjuvant chemotherapy (ACT) analyses. Flow cytometry and multiplex immunostaining were used to characterize CD226+CD8+ T cells.
Results
CD226+CD8+ T cells predicted favorable outcomes in patients undergoing curative resection for GC. GC patients with high CD226+CD8+ T cell infiltration benefitted more from adjuvant chemotherapy. CD155 is upregulated in GC tissues and is associated with decreased intra-tumoral CD226+CD8+ T cell infiltration. The combination of intra-tumoral CD226+CD8+ T cells and CD155 is a strong prognostic predictor in patients with GC.
Conclusion
CD226+CD8+ T cells may represent a novel therapeutic target and a useful marker of prognosis and therapeutic response in patients with GC.
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Data availability
The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
Abbreviations
- ACT:
-
Adjuvant chemotherapy
- GC:
-
Gastric cancer
- mIHF:
-
Multiple immunofluorescence
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Acknowledgements
We thank Dr. Zhen Xiang and Dr. Siyuan Liang for their helpful discussion and technical assistance.
Funding
National Natural Science Foundation of China (81902392); Clinical Research Plan of SHDC (No. SHDC2020CR3033B).
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YZ: performed the experiments; YZ: analyzed the data and prepared the manuscript; YZ, ZZ, JG and HH: provided the samples. YZ and HH: wrote the paper; YZ, ZZ, JG, YH and HH: commented on the study and revised the paper; HH: supervised the project.
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Zhang, Y., Zhao, Zx., Gao, Jp. et al. Tumor-infiltrating CD226+CD8+ T cells are associated with postoperative prognosis and adjuvant chemotherapeutic benefits in gastric cancer patients. J Cancer Res Clin Oncol 149, 4381–4389 (2023). https://doi.org/10.1007/s00432-022-04346-x
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DOI: https://doi.org/10.1007/s00432-022-04346-x