Abstract A212: Expanded CD8+PD-1+ T-cell and TCR repertoire signatured clinical response of adoptive T-cell immunotherapy in advanced pancreatic cancers

Abstract

Abstract Purpose: Advanced pancreatic cancer(APC) has remained challenging to treat effectively. This study aimed to explore the biologic antitumor activities of sorted CD8+PD-1+T-cells expanded from peripheral blood mononuclear cells (PBMCs) and analyze the prognostic values of fold expansion capacity of functional CD8+PD-1+T-cells and TCR repertoire after ex vivo expansion. Experimental Design: 25 selected APC patients who had been previously confirmed with improved clinical response based on chemotherapeutic S-1 plus adoptive T-cell immunotherapy were further stratified to identify the biologically molecular mechanism of expanded CD8+PD-1+T-cell and restored TCR repertoire on post-infused patients’ peripheral blood T lymphocytes phenotype and subsequent association with clinical responses. Results: The harvested PMBCs were expanded ex vivo under the cytokines’ stimulation. The induced CD3+, CD3+CD4+, CD3+CD8+T-cells components reached the peak value in 15 days. CD8+T-cells exhibited enhanced expression of PD-1, LAG-3, and TIM-3 after ex vivo expansion except for 4-1BB. Survival analysis showed that patients with ratio of post/pre CD8+PD-1+T-cells more than 2 had significantly favorable overall survival (OS) (median OS time 238 days versus 142 days, P=0.024) and progressive-free survival (PFS) (median PFS time 180 days vs 85 days, P=0.002). The sorted CD8+PD-1+T-cells were featured by enhanced antitumor activities with the appearance of increased release of IFN-γ secretion and up-regulation of 4-1BB after co-culture with autologous tumor cell line. TCR repertoire diversity simultaneously rose during the ex vivo expansion in which increased unique clones could result in peripheral blood immunologically phenotypic improvements represented by CD8+ enhancement and CD8+/CD28- decline. Moreover, TCR increased unique clones were associated with significantly favorable OS (median OS time 216 days versus 112 days, P=0.031) and PFS (median PFS time 166 days vs 79 days, P=0.043) and the alteration of CD8+PD-1+T-cells (r2=0.464, P=0.001). Conclusion: This study showed that CD8+PD-1+T-cells after ex vivo expansion in 15 days could be identified as the tumor-reactive cells. The present discoveries were filled with that expanded CD8+PD-1+T-cells and restored TCR repertoire were significantly associated with clinical responses in APC. Citation Format: Guoliang Qiao. Expanded CD8+PD-1+ T-cell and TCR repertoire signatured clinical response of adoptive T-cell immunotherapy in advanced pancreatic cancers [abstract]. In: Proceedings of the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; Sept 30-Oct 3, 2018; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2019;7(2 Suppl):Abstract nr A212.