The mutational load and a T-cell inflamed tumour phenotype identify ovarian cancer patients rendering tumour-reactive T cells from PD-1+ tumour-infiltrating lymphocytes
| Autor: | Sandra Hervas-Stubbs, Ibon Tamayo-Uria, Pablo Sarobe, Uxua Mancheño, Antonio González-Martín, Edurne Elizalde, José Manuel Aramendía, Juan C. Muruzabal, Mariano Ponz-Sarvise, Francisco Guillén-Grima, Juan José Lasarte, Julia Alcaide, Enrique Conde, David Garcia-Ros, Carlos E. de Andrea, Diego Salas-Benito, José Ángel Mínguez, Jose Amores-Tirado |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Cancer Research
T cell Programmed Cell Death 1 Receptor chemical and pharmacologic phenomena CD8-Positive T-Lymphocytes Immunofluorescence Article Flow cytometry 03 medical and health sciences 0302 clinical medicine Lymphocytes Tumor-Infiltrating medicine Biomarkers Tumor Humans 030304 developmental biology Retrospective Studies Ovarian Neoplasms 0303 health sciences medicine.diagnostic_test business.industry CD137 hemic and immune systems medicine.disease Prognosis Phenotype Epithelium Gene Expression Regulation Neoplastic medicine.anatomical_structure Oncology 030220 oncology & carcinogenesis Cancer research Tumour immunology Female Immunotherapy business Ovarian cancer CD8 Follow-Up Studies |
| Zdroj: | British Journal of Cancer |
| ISSN: | 1532-1827 0007-0920 |
| Popis: | Background Adoptive immunotherapy with tumour-infiltrating lymphocytes (TIL) may benefit from the use of selective markers, such as PD-1, for tumour-specific T-cell enrichment, and the identification of predictive factors that help identify those patients capable of rendering tumour-reactive TILs. We have investigated this in ovarian cancer (OC) patients as candidates for TIL therapy implementation. Methods PD-1− and PD-1+ CD8 TILs were isolated from ovarian tumours and expanded cells were tested against autologous tumour cells. Baseline tumour samples were examined using flow cytometry, multiplexed immunofluorescence and Nanostring technology, for gene expression analyses, as well as a next-generation sequencing gene panel, for tumour mutational burden (TMB) calculation. Results Tumour-reactive TILs were detected in half of patients and were exclusively present in cells derived from the PD-1+ fraction. Importantly, a high TIL density in the fresh tumour, the presence of CD137+ cells within the PD-1+CD8+ TIL subset and their location in the tumour epithelium, together with a baseline T-cell-inflamed genetic signature and/or a high TMB, are features that identify patients rendering tumour-reactive TIL products. Conclusion We have demonstrated that PD-1 identifies ovarian tumour-specific CD8 TILs and has uncovered predictive factors that identify OC patients who are likely to render tumour-specific cells from PD-1+ TILs. |
| Databáze: | OpenAIRE |
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