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Ex vivo analysis of pancreatic cancer-infiltrating T lymphocytes reveals that ENO-specific Tregs accumulate in tumor tissue and inhibit Th1/Th17 effector cell functions.

Abstract
Pancreatic cancer (PC) is an aggressive disease with dismal prognosis. Surgical resection is the recommended treatment for long-term survival, but patients with resectable PC are in the minority (with a 5-year survival rate of 20 %). Therefore, development of novel therapeutic strategies, such as anti-PC immunotherapy, is crucial. α-Enolase (ENO1) is an enzyme expressed on the surface of pancreatic cancer cells and is able to promote cell migration and cancer metastasis. The capacity of ENO1 to induce an immune response in PC patients renders it a true tumor-associated antigen. In this study, we characterized the effector functions of ENO1-specific T cells isolated from PC patients, and we specifically evaluated the successful role of intra-tumoral T helper 17 (Th17) cells and the inhibitory role of regulatory T (Tregs) cells in respectively promoting or reducing the cancer-specific immune response. In this ex vivo study, we have demonstrated, for the first time, that ENO1-specific Th17 cells have a specific anti-cancer effector function in PC patients, and that there are decreased levels of these cells in cancer compared to healthy mucosa. Conversely, there are elevated levels of ENO1-specific Tregs in PC patients which lead to inhibition of the antigen-specific effector T cells, thus highlighting a possible role in promoting PC progression. These results may be relevant for the design of novel immunotherapeutic strategies in pancreatic cancer.
AuthorsAmedeo Amedei, Elena Niccolai, Marisa Benagiano, Chiara Della Bella, Fabio Cianchi, Paolo Bechi, Antonio Taddei, Lapo Bencini, Marco Farsi, Paola Cappello, Domenico Prisco, Francesco Novelli, Mario Milco D'Elios
JournalCancer immunology, immunotherapy : CII (Cancer Immunol Immunother) Vol. 62 Issue 7 Pg. 1249-60 (Jul 2013) ISSN: 1432-0851 [Electronic] Germany
PMID23640603 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Biomarkers, Tumor
  • DNA-Binding Proteins
  • Tumor Suppressor Proteins
  • ENO1 protein, human
  • Phosphopyruvate Hydratase
Topics
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor (immunology)
  • CD4-Positive T-Lymphocytes (immunology)
  • CD8-Positive T-Lymphocytes (immunology)
  • Cells, Cultured
  • DNA-Binding Proteins (immunology)
  • Female
  • Humans
  • Male
  • Middle Aged
  • Pancreatic Neoplasms (immunology)
  • Phosphopyruvate Hydratase (immunology)
  • T-Lymphocytes, Regulatory (immunology)
  • Th1 Cells (immunology, metabolism)
  • Th17 Cells (immunology, metabolism)
  • Tumor Suppressor Proteins (immunology)

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