Circulating regulatory T cell subsets predict overall survival of patients with unresectable pancreatic cancer

Most patients with pancreatic ductal adenocarcinoma (PDAC) have unresectable cancers with a dismal prognosis, in which cohort chemotherapy is the primary treatment. T cell immune adaption is critical for tumor immune escape and prognosis of this disease. The present study aimed to determine the correlation between peripheral T cell subset distribution in patients with unresectable PDAC and their response to chemotherapy. Two hundred and twelve patients with unresectable PDAC were included whose blood samples were collected for analysis of T cell subsets, including CD3(+), CD4(+), CD8(+), CD8(+)CD28(+) and CD4(+) CD25(+)CD127 T cells by flow cytometry before and after gemcitabine-based chemotherapy. Enzyme-linked immunosorbent assay was used to detect the expression levels of tumor growth factor (TGF)-beta 1, interleukin (IL)-6 and IL-17A in the patients before and after chemotherapy. Univariate and multivariate analyses found that an initial CD4/CD8 ratio or T regulatory (Treg) cell level before any treatment was associated with the prognosis of unresectable PDAC. After two cycles of chemotherapy, there was no significant change in percentages of T cell subsets, except elevation to a higher level of CD3(+) T cells. Decreased Tregs or CD4/CD8 ratio after two cycles of chemotherapy predicts a longer overall survival (OS). Levels of Tregs in stable disease (SD) and partial remission (PR) cases significantly decreased after chemotherapy, but increased in progressive disease (PD) patients. There was no correlation between Tregs and the expression level of either TGF-beta 1 or IL-6. IL-17A expression was elevated in Treg-decreased patients, whereas IL-17A was reduced in Treg-increased patients after chemotherapy. The circulating signature of T cell subsets can predict OS and chemotherapeutic response in patients with unresectable PDAC, and may be attributable to the plasticity of T cell subsets.