Stamova, Slava and Ott-Rotzer, Birgitta and Smetak, Heiko and Schaeffler, Katharina and Eder, Ruediger and Fink, Irina and Hoffmann, Petra and Reichert, Torsten E. and Beckhove, Philipp and Spanier, Gerrit (2021) 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. JOURNAL OF IMMUNOLOGICAL METHODS, 496: 113086. ISSN 0022-1759, 1872-7905
Full text not available from this repository. (Request a copy)Abstract
Rare subpopulations of tumor antigen-reactive memory T cells, which actively secrete type-1 effector cytokines, particularly TNF-alpha 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-alpha T+ cells were CD4(+) T helper cells while IFN-gamma+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-alpha 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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | INFILTRATING LYMPHOCYTES; BONE-MARROW; SELECTIVE EXPRESSION; MEMORY PRECURSOR; TRANSFER THERAPY; PROGNOSTIC VALUE; CANCER-PATIENTS; EFFECTOR; CD8(+); NAIVE; Tumor-reactive T cells; TNF-alpha secretion; T cell culture; OSCC; Immunotherapy |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie) Medicine > Lehrstuhl für Mund-, Kiefer- und Gesichtschirurgie Medicine > Zentren des Universitätsklinikums Regensburg > Regensburger Centrum für Interventionelle Immunologie (RCI) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 12 Jul 2022 05:06 |
| Last Modified: | 12 Jul 2022 05:06 |
| URI: | https://pred.uni-regensburg.de/id/eprint/45687 |
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