Data from CXCL10 Recruitment of γδ T Cells into the Hypoxic Bone Marrow Environment Leads to IL17 Expression and Multiple Myeloma Progression

• DOI: 10.1158/2326-6066.c.6864868.v1
• Publication Date: 2023-10-04T07:22:26Z
• Authors: Jingya Wang; Ziyi Peng; Jing Guo; Yixuan Wang; Sheng Wang; Hongmei Jiang; Mengqi Wang; Ying Xie; Xin Li; Meilin Hu; Yangyang Xie; Hao Cheng; Tiantian Li; Linchuang Jia; Jia Song; Yafei Wang; Jian Hou; Zhiqiang Liu

<div>Abstract<p>In multiple myeloma (MM), bone marrow stromal cells (BMSC) shape a unique niche within the marrow, promoting T-cell dysfunction and driving MM progression; however, precise underlying mechanisms remain elusive. Here, we show that BMSC-mediated reprogramming of led to heightened production CXCL10. CXCL10 orchestrated recruitment γδ T into this was observed in both Vk*MYC 5TGM1 mouse models MM, as well patients experiencing refractory or relapsed MM. Furthermore, dysfunctional exhibited increased PD-1 expression IL17 production. In model, MM–associated lesions mortality were markedly alleviated <i>Tcrd<sup>−/−</sup></i> mice, disease progression could be rescued these mice upon transplantation expanded from wild-type but not <i>Il17<sup>−/−</sup></i> mice. Mechanistically, hypoxic microenvironment prevailing stimulated steroid receptor coactivator 3 (SRC-3) cells, which turn interacted with transcriptional factor RORγt, <i>Il17</i> transcription. Pharmacologic inhibition SRC-3 utilizing SI-2 effectively suppressed <i>Il17A</i> leading alleviation murine enhancing anti–multiple efficacy bortezomib. Our results illuminated microenvironment's involvement provoking throughout suggest promising strategy enhance effectiveness immunotherapies targeting cells.</p></div>