S1PR4 ablation reduces tumor growth and improves chemotherapy via CD8+ T cell expansion - Forschungsportal der Justus-Liebig-Universität Gießen:

Journalartikel

S1PR4 ablation reduces tumor growth and improves chemotherapy via CD8+ T cell expansion

Autorenliste: Olesch, Catherine; Sirait-Fischer, Evelyn; Berkefeld, Matthias; Fink, Annika F.; Susen, Rosa M.; Ritter, Birgit; Michels, Birgitta E.; Steinhilber, Dieter; Greten, Florian R.; Savai, Rajkumar; Takeda, Kazuhiko; Bruene, Bernhard; Weigert, Andreas

Jahr der Veröffentlichung: 2020

Seiten: 5461-5476

Zeitschrift: The Journal of Clinical Investigation

Bandnummer: 130

Heftnummer: 10

ISSN: 0021-9738

eISSN: 1558-8238

Open Access Status: Green

DOI Link: https://doi.org/10.1172/JCI136928

Verlag: American Society for Clinical Investigation

Abstract:
Tumor immunosuppression is a limiting factor for successful cancer therapy. The lipid sphingosine-1-phosphate (SIP), which signals through 5 distinct G protein-coupled receptors (S1PR1-5), has emerged as an important regulator of carcinogenesis. However, the utility of targeting SW in tumors is hindered by S1P's impact on immune cell trafficking. Here, we report that ablation of the immune cell-specific receptor S1PR4, which plays a minor role in immune cell trafficking, delayed tumor development and improved therapy success in murine models of mammary and colitis-associated colorectal cancer through increased CD8' T cell abundance. Transcriptome analysis revealed that S1PR4 affected proliferation and survival of CD8(+) T cells in a cell-intrinsic manner via the expression of PIK3AP1 and Lta4h. Accordingly, PIK3AP1 expression was connected to increased CD8(+)T cell proliferation and clinical parameters in human breast and colon cancer. Our data indicate a so-faruna ppreciated tumor promoting role of SiP by restricting CD8(+) cell expansion via S1PR4.

Zitierstile

Harvard-Zitierstil: Olesch, C., Sirait-Fischer, E., Berkefeld, M., Fink, A., Susen, R., Ritter, B., et al. (2020) S1PR4 ablation reduces tumor growth and improves chemotherapy via CD8+ T cell expansion, The Journal of Clinical Investigation, 130(10), pp. 5461-5476. https://doi.org/10.1172/JCI136928

APA-Zitierstil: Olesch, C., Sirait-Fischer, E., Berkefeld, M., Fink, A., Susen, R., Ritter, B., Michels, B., Steinhilber, D., Greten, F., Savai, R., Takeda, K., Bruene, B., & Weigert, A. (2020). S1PR4 ablation reduces tumor growth and improves chemotherapy via CD8+ T cell expansion. The Journal of Clinical Investigation. 130(10), 5461-5476. https://doi.org/10.1172/JCI136928

Zitierstile

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