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
Stamova S, Ott-Rotzer B, Smetak H, Schaeffler K, Eder R, Fink I, Hoffmann P, Reichert TE, Beckhove P, Spanier G (2021)
Publication Type: Journal article
Publication year: 2021
Journal
Book Volume: 496
Article Number: 113086
DOI: 10.1016/j.jim.2021.113086
Abstract
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.
Involved external institutions
Germany (DE)How to cite
APA:
Stamova, S., Ott-Rotzer, B., Smetak, H., Schaeffler, K., Eder, R., Fink, I.,... Spanier, G. (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. https://doi.org/10.1016/j.jim.2021.113086
MLA:
Stamova, Slava, et al. "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 (2021).
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