In contrast to the general belief that pancreatic ductal adenocarcinoma is a poorly immunogenic tumor, we found cumulative evidence for an adaptive immune response in this aggressive cancer type. Immunohistochemistry reveals prominent T-cell infiltrates in the majority (~ 70%) of tumor biopsies, and these tumor-infiltrating lymphocytes (TILs) can be isolated and expanded ex vivo with similar efficiency as those isolated from melanoma. Furthermore, comparison of the T-cell receptor repertoire between TIL and PBMC isolates from patients points at the selective expansion of T-cell subsets in the tumors. Finally, in ~ 50% of tumor specimen, T-cell infiltration is accompanied by the presence of tertiary lymphoid structures that comprise areas rich in CD3+ T-cells and CD208+ dendritic cells as well as areas rich in B-cells and follicular dendritic cells.
Based on these findings, our current efforts aim at:
- Evaluating neoadjuvant treatment with agonist immunostimulatory antibodies as a means to mobilize this pre-existing immune response in patients with primary resectable disease*
- Analysis of the anti-tumor reactivity and antigen-specificity of TCR-species that are prominently enriched in the tumor as compared to PBMC.
- Exploration of TIL therapy for treatment of recurrent disease.
* Clinical trial in context of FP7 EU IACT program; Immunostimulatory Antibodies for Cancer Treatment
Citation Format: Rienk Offringa, Isabel Poschke, Michael Volkmar, Oliver Strobel, Frank Bergmann, Niels Halama, Dirk Jäger, Ugur Sahin, Markus Büchler. Towards implementation of T-cell therapy in pancreatic cancer. [abstract]. In: Proceedings of the CRI-CIMT-EATI-AACR Inaugural International Cancer Immunotherapy Conference: Translating Science into Survival; September 16-19, 2015; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(1 Suppl):Abstract nr IA46.
- ©2016 American Association for Cancer Research.