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. 2017 Aug 10;7(1):7848.
doi: 10.1038/s41598-017-08479-9.

Prognostic Value of Programmed Cell Death Protein 1 Expression on CD8+ T Lymphocytes in Pancreatic Cancer

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Free PMC article

Prognostic Value of Programmed Cell Death Protein 1 Expression on CD8+ T Lymphocytes in Pancreatic Cancer

Tao Shen et al. Sci Rep. .
Free PMC article

Abstract

Pancreatic cancer is one of the most aggressive malignancies and has a highly immunosuppressive tumour microenvironment. Immune checkpoint blockade has led to remarkable and durable objective responses in a number of malignancies and antibody-based strategies targeting programmed cell death protein 1 (PD-1) are showing promise where traditional modalities of surgery, radiotherapy, and chemotherapy have failed. In this study, we examined the clinical value of PD-1 protein expression by CD8+ peripheral T lymphocytes or tumour-infiltrating T lymphocytes (TILs) in pancreatic ductal adenocarcinoma (PDAC). Expression of PD-1 protein on CD8+ TILs correlated with overall survival and clinicopathological characteristics such as clinical stage, N classification, and M classification. Similar findings were observed for the expression of PD-1 protein on peripheral CD8+ T cells, whereas its expression on peripheral CD4+ T cells showed no significance. Comparison of the levels of PD-1 protein expressed by peripheral CD8+ T cells before and 4 weeks after surgery indicated that preoperative and postoperative status of peripheral PD-1 expression was unchanged. Our findings showed that PD-1 protein expressed by peripheral or tumour-infiltrated CD8+ T cells was a promising biomarker for diagnosis and prognosis in PDAC and might help guide future immunotherapies.

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Figure 1
Figure 1
Level of PD-1 expression on CD8+ T cells in PDAC tissue samples and its correlation with overall survival rate in pancreatic ductal adenocarcinoma patients. (A) Tissues derived from surgical resection of PDAC patients were stained with antibodies to human CD8 (red) (a) and PD-1 (green) (b) and counterstained with DAPI (blue) (c). Isotype control antibodies for anti-PD-1 and anti-CD8 were included in each experiment (e, f). The merged graph (d) shows that the pancreatic duct (dotted line) was mainly infiltrated with CD8+ T cells (arrows) whereas stroma was mainly infiltrated with PD-1+ CD8+ T cells (arrowheads) (original magnification, ×400). A representative experiment is shown in B. Quantitative measurement of CD8+ and PD-1+ CD8+ Tumour-infiltrating lymphocytes (TILs) was performed in at least four random high power fields (×400), and the expression level of PD-1 on CD8+ TILs was calculated as follows: expression level, % = (PD-1+ CD8+ TILs/CD8+ TILs) × 100. For quantitative variables, the median was used as a cut-off. Mean (±SD) number of infiltrated PD-1+ CD8+ T cells and CD8+ T cells and mean (±SD) expression of PD-1 protein on tumour-infiltrating CD8+ T cells from 94 paired samples of PDAC tumour tissues and adjacent non-tumour tissues is shown in C (paired-samples T-test, **P < 0.001). For the analysis of overall survival or disease-free survival, high and low levels were defined using the median level of PD-1 expression on tumour-infiltrated CD8+ T cells as the cut-off value. Survival analysis was performed using the Kaplan–Meier method and log-rank test. (D) High expression level of PD-1 on CD8+ T cells in tumour tissue was significantly correlated with poor survival of PDAC patients. Correlation between PD-1 expression and overall survival rate in PDAC patients was independent of clinical stage (E) and status of lymphatic metastasis (F).
Figure 2
Figure 2
PD-1 protein expression is increased on peripheral CD8+ T cells but not on peripheral CD4+ T cells in patients with pancreatic ductal adenocarcinoma. The levels of PD-1 protein expressed by peripheral CD8+ T lymphocytes (A) and peripheral CD4+ T lymphocytes (B) in 68 patients with PDAC, 40 patients with intraductal papillary mucinous neoplasm (IPMN), and 20 healthy donors were detected by flow cytometry. Graphs show quantification of FACS data. Flow cytometry pseudo colour of lymphocytes and CD3+ CD8+ (A) or CD3+ CD4+ (B) cells and representative smoothing pseudo colour of PD-1+ cells are displayed. Data shown are mean ± standard deviation, **P < 0.001. (C) ROC curve for the correlation of PD-1 expression on peripheral CD8+ T cells with PDAC. Area under the curve is 0.8607 (95% confidence interval 0.7938 to 0.9276), P < 0.001. The cut-off value of >47.81% PD-1 expression on CD8+ T cells is designated by the red triangle. (D) There was no significant difference in the level of PD-1 expression between preoperative and 4-week postoperative peripheral CD8+ T lymphocytes. Wilcoxon matched-pairs signed rank test; P = 0.498.

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References

    1. Siegel, R. L., Miller, K. D. & Jemal, A. Cancer statistics, 2016. CA Cancer J Clin. 66, 7–30. doi:10.3322/caac.21332. Epub 22016 Jan 21337 (2016). - PubMed
    1. Wolfgang, C. L. et al. Recent progress in pancreatic cancer. CA Cancer J Clin. 63, 318–348. doi:310.3322/caac.21190. Epub 22013 Jul 21115 (2013). - PMC - PubMed
    1. Morganti, A. G. et al. A systematic review of resectability and survival after concurrent chemoradiation in primarily unresectable pancreatic cancer. Ann Surg Oncol. 17, 194-205 doi:110.1245/s10434-10009-10762-10434. Epub 12009 Oct 10424 (2010). - PubMed
    1. Hartwig W, Werner J, Jager D, Debus J, Buchler MW. Improvement of surgical results for pancreatic cancer. Lancet Oncol. 2013;14:e476–485. doi: 10.1016/S1470-2045(13)70172-4. - DOI - PubMed
    1. Van Laethem, J. L. et al. New strategies and designs in pancreatic cancer research: consensus guidelines report from a European expert panel. Ann Oncol. 23, 570–576 doi:510.1093/annonc/mdr1351. Epub 2011 Aug 1091 (2012). - PubMed

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