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Neoepitope targets of tumour-infiltrating lymphocytes from patients with pancreatic cancer.
- Source :
-
British journal of cancer [Br J Cancer] 2019 Jan; Vol. 120 (1), pp. 97-108. Date of Electronic Publication: 2018 Oct 31. - Publication Year :
- 2019
-
Abstract
- Background: Pancreatic cancer exhibits a poor prognosis and often presents with metastasis at diagnosis. Immunotherapeutic approaches targeting private cancer mutations (neoantigens) are a clinically viable option to improve clinical outcomes.<br />Methods: 3/40 TIL lines (PanTT26, PanTT39, PanTT77) were more closely examined for neoantigen recognition. Whole-exome sequencing was performed to identify non-synonymous somatic mutations. Mutant peptides were synthesised and assessed for antigen-specific IFN-γ production and specific tumour killing in a standard Cr51 assay. TIL phenotype was tested by flow cytometry. Lymphocytes and HLA molecules in tumour tissue were visualised by immunohistochemistry.<br />Results: PanTT26 and PanTT39 TILs recognised and killed the autologous tumour cells. PanTT26 TIL recognised the KRAS <subscript>G12v</subscript> mutation, while a PanTT39 CD4 <superscript>+</superscript> TIL clone recognised the neoepitope (GLLRYWRTERLF) from an aquaporin 1-like protein (gene: K7N7A8). Repeated stimulation of TILs with the autologous tumour cells line lead to focused recognition of several mutated targets, based on IFN-γ production. TILs and corresponding PBMCs from PanTT77 showed shared as well as mutually exclusively tumour epitope recognition (TIL-responsive or PBMC-responsive).<br />Conclusion: This study provides methods to robustly screen T-cell targets for pancreatic cancer. Pancreatic cancer is immunogenic and immunotherapeutic approaches can be used to develop improved, targeted therapies.
- Subjects :
- Aquaporin 1 genetics
Aquaporin 1 immunology
Cell Line, Tumor
Cytotoxicity, Immunologic immunology
Flow Cytometry
Humans
Interferon-gamma immunology
Lymphocytes, Tumor-Infiltrating pathology
Pancreatic Neoplasms pathology
Epitopes immunology
Interferon-gamma genetics
Lymphocytes, Tumor-Infiltrating immunology
Pancreatic Neoplasms immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1532-1827
- Volume :
- 120
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- British journal of cancer
- Publication Type :
- Academic Journal
- Accession number :
- 30377343
- Full Text :
- https://doi.org/10.1038/s41416-018-0262-z