High percentage of circulating PD-1+ T cells correlated with malignancy and recurrence of peritoneal adenocarcinoma

Abstract

Abstract Background Immune checkpoint blockade with anti-PD-1 antibody has become a hot topic for the treatment of human malignancies. Here, we seek the percentage of PD-1 + T cells whether predicting the malignancy and recurrence of peritoneal adenocarcinoma, and go further to investigate the positive percentage of PD-1 whether correlate with the progression-free survival (PFS) after initial surgery. Method Peripheral blood (PB) from 80 patients with peritoneal adenocarcinoma and 38 health controls are recruited, subject to multicolor flow cytometric analysis of the peripheral PD-1 and Tim-3 positive percentages. 40 cases of peritoneal adenocarcinoma tissue samples are also collected, the method of immunohistochemistry is used to detect the positive percentage of PD-1 in the tissue section. The enrolled peritoneal adenocarcinoma patients are divided by clinical stage (TNM), histological grade, and recurrence interval (less than 6 months, greater than two years). Result Compare with normal control’s PB, CD4 + T cells, CD8 + T cells, Treg cells, IL-6 and IL-10 exhibit higher frequencies in peritoneal adenocarcinoma group. It also discovers that peritoneal adenocarcinoma patients present higher levels of circulating PD-1 + lymphocytes, Tim-3 + lymphocytes, PD-1 + T lymphocytes, PD-1 + CD4 + T lymphocytes and PD-1 + CD8 + T lymphocytes. CD4 + T lymphocytes and PD-1 + T lymphocytes in circulation are correlated with recurrence interval after initial surgery. In the PB, circulating PD-1 + T lymphocytes and PD-1 + CD4 + T lymphocytes also have closely linked with the histologic grade of peritoneal adenocarcinoma. In the tissue section, the significantly increased percentage of PD-1 expressed on the tumor-infiltrating lymphocytes (TILs) is found in the well/moderate grade than the low grade. And the PD-1 also correlates with lymph node metastasis in peritoneal adenocarcinoma tissues. The level of PD-1 correlates with the clinical outcome of peritoneal adenocarcinoma. Higher percentage of PD-1 correlates with the shorter PFS. Conclusion PD-1 may have a good predictive value for the immunotherapy of peritoneal adenocarcinoma, and act as the prognostic factor for the PFS.