Characterization and ex vivo expansion of rare in situ cytokine secreting T cell populations from tumor tissue and blood of oral squamous cell carcinoma patients
| Autor: | Petra Hoffmann, Irina Fink, Rüdiger Eder, Birgitta Ott-Rötzer, Heiko Smetak, Torsten E. Reichert, Katharina Schäffler, Slava Stamova, Philipp Beckhove, Gerrit Spanier |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Adult
Male 0301 basic medicine medicine.medical_treatment T cell Immunology Cell Separation CD8-Positive T-Lymphocytes Interferon-gamma 03 medical and health sciences Lymphocytes Tumor-Infiltrating 0302 clinical medicine Cancer immunotherapy Antigens Neoplasm medicine Humans Immunology and Allergy Cells Cultured Aged Cell Proliferation Squamous Cell Carcinoma of Head and Neck Tumor Necrosis Factor-alpha Chemistry T-Lymphocytes Helper-Inducer Immunotherapy Middle Aged Phenotype 030104 developmental biology medicine.anatomical_structure Cytokine Cell culture Cancer research Female Mouth Neoplasms Immunologic Memory Memory T cell CD8 Ex vivo 030215 immunology |
| Zdroj: | Journal of Immunological Methods. 496:113086 |
| ISSN: | 0022-1759 |
| Popis: | Rare subpopulations of tumor antigen-reactive memory T cells, which actively secrete type-1 effector cytokines, particularly TNF-α in situ, possess anti-tumor activity and prognostic relevance. These cells are relevant for cancer immunotherapy; however, their low frequencies make them difficult to study and novel protocols for their culture and expansion ex vivo are needed. Here, we studied the presence of T cells secreting type-1 cytokines (Cy+T cells) in the blood and tumors of 24 patients with oral squamous cell carcinomas (OSCC) and explored possibilities for their isolation and expansion. More than 90% of OSCC patients contained enriched numbers Cy+T cells in the blood and tumors compared to healthy donors in which these were hardly detectable. The majority of TNF-α+T cells were CD4+ T helper cells while IFN-γ+TIL were predominantly CD8+. Cy+T helper cells in the blood were early-differentiated memory T cells while Cy+TIL and Cy+CD8+T cells showed advanced-differentiated memory T cell phenotypes. We explored different conditions for their in vitro culture and found that Cy+T cells can be efficiently expanded in vitro to similar levels as Cy-T cells and after expansion maintained their TNF-α secreting capacity. However, for optimal expansion they required specific culture conditions to support the maintenance of stem-like and central memory T cell phenotype. In conclusion, we show that Cy+T cells are enriched in OSCC patients and report a novel cell culture protocol optimized to specifically expand and functionally maintain these cells for further functional characterization or for their exploitation in immunotherapy of OSCC. |
| Databáze: | OpenAIRE |
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