Expansion of tumor-infiltrating lymphocytes (TIL) from human pancreatic tumors. Issue 1 (18th October 2016)

• Record Type: Journal Article
• Authors: Hall, MacLean; Liu, Hao; Malafa, Mokenge; Centeno, Barbara; Hodul, Pamela J.; Pimiento, José; Pilon-Thomas, Shari; Sarnaik, Amod A.
• Is Part Of: Journal for immunotherapy of cancer. Volume 4:Issue 1(2016)
• Publication Date: 2016-10-18
• Subjects: Pancreatic cancer -- T cells -- Adoptive cell therapy -- Tumor infiltrating lymphocytes (TIL); Cancer -- Immunotherapy -- Periodicals; Cancer -- Immunological aspects -- Periodicals; Tumors -- Immunological aspects -- Periodicals; Immunotherapy -- Periodicals; 616.99406105
• DOI: 10.1186/s40425-016-0164-7
• Languages: English
• ISSNs: 2051-1426

Abstract

Abstract : Background: We evaluated whether tumor infiltrating lymphocytes (TIL) could be expanded from surgically resected tumors from pancreatic cancer patients. Methods: Tumors were resected from pancreatic cancer patients. Tumors were minced into fragments and cultured in media containing high dose interleukin-2 (IL-2) for up to 6 weeks. T cell phenotype, activation markers, and reactivity were measured. Results: TIL expansion was measured in 19 patient samples. The majority of these TIL were CD4 + T cells and were highly activated. Purified CD8 + T cells produced IFN-γ in response to HLA-matched pancreatic tumor targets. PD-1 blockade and 4-1BB stimulation were demonstrated as effective strategies to improve effective TIL yield, including the production of tumor-reactive pancreatic TIL. Conclusions: TIL expanded from pancreatic tumors are functional and able to respond to pancreatic tumor associated antigens. PD-1 blockade, 41BB stimulation, and CD8 + T cell enrichment are effective strategies to improve TIL yield and tumor reactivity. These results support the development of adoptive cell therapy strategies using TIL for the treatment of pancreatic cancer.