Profiling of circulating T-cells with prognostic and predictive value in early and advanced stage PDAC

Pancreatic Ductal Adenocarcinoma (PDAC) is a lethal malignancy with few treatment options. Despite the promising results of immunotherapy in various solid cancers, the efficacy of immunotherapy in PDAC is poor. Therefore, deciphering immune responses is pivotal for the development of novel combinatorial immunotherapies. Here, we analyzed the immunophenotypic profile of circulating distinct T-cell subtypes and their prognostic value in early and advanced/metastatic PDAC patients by using multicolor flow-cytometry. We observed higher percentages of progenitor exhausted TCF1 ⁺ PD1 ⁺ T-cells in PDAC patients compared to healthy donors. Notably, increased TCF1 ⁺ PD1 ⁺ T-cells were correlated with prolonged survival (CD3 ⁺ CD4 ⁺ : NR vs. 277 days, p=0.0041 and CD3 ⁺ CD8 ⁺ : NR vs. 390 days, p=0.042) only in early but not in advanced stage PDAC patients. In addition, expression of PD-1 on CD4 ⁺ and CD8 ⁺ T-effector cells has significant prognostic value. For patients with locally advanced/ metastatic stage, CD57 expression on TCF1 ⁺ PD-1 ⁺ T-cells (PFS: 260 vs. 60 days, p= 0.0063 ; OS: 271 vs. 90 days, p= 0.003) was found to be a promising prognostic biomarker of response. Overall, this study provides new evidence on the role of circulating T cells as prognostic biomarkers for different stages of PDAC patients which could improve patient classification for future implementation of immunotherapeutic approaches.