Journal article
Authors list: 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
Publication year: 2020
Pages: 5461-5476
Journal: The Journal of Clinical Investigation
Volume number: 130
Issue number: 10
ISSN: 0021-9738
eISSN: 1558-8238
Open access status: Green
DOI Link: https://doi.org/10.1172/JCI136928
Publisher: 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.
Citation Styles
Harvard Citation style: 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 Citation style: 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
Keywords
CYSTEINYL LEUKOTRIENES; SPHINGOSINE-1-PHOSPHATE
