Regulation of tumor immune suppression and cancer cell survival by CXCL1/2 elevation in glioblastoma multiforme.

Jiemiao Hu, Qingnan Zhao, Ling-Yuan Kong, Jian Wang, Jun Yan, Xueqing Xia, Zhiliang Jia, Amy B Heimberger, Shulin Li

Science advances 2021 Jan

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The invasiveness and high immune suppression of glioblastoma multiforme (GBM) produce poor survival of afflicted patients. Unfortunately, in the past decades, no therapeutic approach has remarkably improved the survival time of patients with GBM. Our analysis of the TCGA database and brain tumor tissue arrays indicated that CXCL1 and CXCL2 overexpression is closely associated with GBM's aggressiveness. Our results showed that elevation of CXCL1 or CXCL2 facilitated myeloid cell migration and simultaneously disrupted CD8+ T cell accumulation at tumor sites, causing accelerated tumor progression. Yet, blockade of CXCL1/2 significantly prevented myeloid-derived suppressor cell migration and thereby increased CD8+ T cell accumulation in vitro and in vivo. CXCL1/2 also promoted the paracrine factor S100A9 and further activated Erk1/2 and p70S60k, whereas blocking CXCL1/2 down-regulated these prosurvival factors. The combination of targeting CXCL1/2 and standard temozolomide chemotherapy improved upon the antitumor efficacy of chemotherapy alone, extending the overall survival time in GBM. Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).

Citation

Jiemiao Hu, Qingnan Zhao, Ling-Yuan Kong, Jian Wang, Jun Yan, Xueqing Xia, Zhiliang Jia, Amy B Heimberger, Shulin Li. Regulation of tumor immune suppression and cancer cell survival by CXCL1/2 elevation in glioblastoma multiforme. Science advances. 2021 Jan;7(5)