CXCL11型
CXCR3型
医学
CD8型
癌症研究
膀胱癌
趋化因子
趋化因子受体
化疗
免疫学
细胞毒性T细胞
CXCL10型
肿瘤科
CXCL9型
内科学
趋化因子受体
CCL5
CCR2型
作者
Tino Vollmer,Stephan Schlickeiser,Leila Amini,Sarah Schulenberg,Desiree J. Wendering,Viqar Showkat Banday,Anke Jurisch,Rebecca Noster,Désirée Kunkel,Nicola Brindle,Ioannis Savidis,Levent Akyüz,Jochen Hecht,Ulrik Stervbo,Toralf Roch,Nina Babel,Petra Reinke,Ola Winqvist,Amir Sherif,Hans-Dieter Volk,Michael Schmueck-Henneresse
出处
期刊:Science Translational Medicine
[American Association for the Advancement of Science (AAAS)]
日期:2021-01-13
卷期号:13 (576)
被引量:15
标识
DOI:10.1126/scitranslmed.abb3735
摘要
Chemotherapy has direct toxic effects on cancer cells; however, long-term cancer control and complete remission are likely to involve CD8+ T cell immune responses. To study the role of CD8+ T cell infiltration in the success of chemotherapy, we examined patients with muscle invasive bladder cancer (MIBC) who were categorized on the basis of the response to neoadjuvant chemotherapy (NAC). We identified the intratumoral CXCR3 chemokine system (ligands and receptor splice variants) as a critical component for tumor eradication upon NAC in MIBC. Through characterization of CD8+ T cells, we found that stem-like T cell subpopulations with abundant CXCR3alt, a variant form of the CXCL11 receptor, responded to CXCL11 in culture as demonstrated by migration and enhanced effector function. In tumor biopsies of patients with MIBC accessed before treatment, CXCL11 abundance correlated with high numbers of tumor-infiltrating T cells and response to NAC. The presence of CXCR3alt and CXCL11 was associated with improved overall survival in MIBC. Evaluation of both CXCR3alt and CXCL11 enabled discrimination between responder and nonresponder patients with MIBC before treatment. We validated the prognostic role of the CXCR3-CXCL11 chemokine system in an independent cohort of chemotherapy-treated and chemotherapy-naïve patients with MIBC from data in TCGA. In summary, our data revealed stimulatory activity of the CXCR3alt-CXCL11 chemokine system on CD8+ T cells that is predictive of chemotherapy responsiveness in MIBC. This may offer immunotherapeutic options for targeted activation of intratumoral stem-like T cells in solid tumors.
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