Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=25514597&cmd=llinks): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests
in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 215
Elevated endoplasmic reticulum stress reinforced immunosuppression in the tumor microenvironment via myeloid-derived suppressor cells #MMPMID25514597
Lee BR; Chang SY; Hong EH; Kwon BE; Kim HM; Kim YJ; Lee J; Cho HJ; Cheon JH; Ko HJ
Oncotarget 2014[Dec]; 5 (23): 12331-45 PMID25514597show ga
The role of endoplasmic reticulum (ER) stress in cancer has been studied in detail, and ER stress is known to increase tumor cell apoptosis, and thus, reduce tumor growth. However, in our study, persistent ER stress induced by multiple administrations of low-dose thapsigargin (Tg) accelerated tumor growth in mice. Tg-mediated ER stress increased the generation of Ly6G+CD11b+ myeloid cells, but did not alter anti-tumor effector T cells. 4-Phenylbutyric acid (4-PBA), a chemical chaperone widely used as an ER stress reducer, attenuated Tg-induced myeloid-derived suppressor cell (MDSC) expansion and tumor growth. Tg-mediated ER stress enhanced the immunosuppressive capacity of tumor-infiltrating MDSCs by increasing expression of ARG1, iNOS, and NOX2, although splenic MDSCs were not affected. Consistent with these results, 4-PBA restored the anti-tumor immune response by regulating inflammatory cytokines such as TNF-alpha and CXCL1/KC, and activated tumor-infiltrating CD8+ T cells that were inhibited by Tg-mediated ER stress. These results suggest that significant ER stress in a tumor-bearing host might induce tumor growth mediated by enhancement of MDSC-mediated suppression. Therefore, ER stress reducers such as 4-PBA could restore anti-tumor immunity by inhibiting suppressive MDSCs that are exacerbated by ER stress.
free
free
free
Oncotarget 2014 ; 5 (23): 12331-45
