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<p>Patients with metastatic renal cell carcinoma treated with immune checkpoint inhibitors or antiangiogenic tyrosine kinase inhibitors may develop resistance driven by gut dysbiosis, which disrupts the MAdCAM-1–α4β7 axis and promotes the recruitment of immunosuppressive IL-17-producing T regulatory (Tr17) cells into tumors. We evaluated soluble MAdCAM-1 (sMAdCAM-1) as a prognostic biomarker in 1,051 patients from three cohorts: JAVELIN Renal 101 (avelumab plus axitinib versus sunitinib), SURF (sunitinib) and NIVOREN (nivolumab after tyrosine kinase inhibitors). In the JAVELIN cohort, baseline sMAdCAM-1 levels &gt;180 ng ml<sup>−1</sup> were associated with significantly improved progression-free survival (13.9 versus 8.4 months, <i>P</i> &lt; 0.01) and overall survival (18 months: 84.2% versus 68.1%, <i>P</i> &lt; 0.01), independent of IMDC risk groups. We validated the prognostic value of sMAdCAM-1 for overall survival in the SURF and NIVOREN cohorts. Notably, low sMAdCAM-1 levels were associated with an immunosuppressive gut microbiota profile dominated by <i>Enterocloster</i> species. Therefore, sMAdCAM-1 deserves further investigations as a biomarker-guided tool for microbiota-targeted interventions.</p>

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Soluble MAdCAM-1 as a biomarker in metastatic renal cell carcinoma

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年1月7日

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  • Carolina Alves Costa Silva,
  • Marc Machaalani,
  • Renee Maria Saliby,
  • Caiwei Zhong,
  • Wanling Xie,
  • Edoardo Pasolli,
  • Gianmarco Piccinno,
  • Cécile Dalban,
  • Marine Fidelle,
  • Aurelia Meurisse,
  • Dewi Vernerey,
  • Gwo-Shu Mary Lee,
  • Roxanne Birebent,
  • Eddy Saad,
  • Clara Steiner,
  • Ronan Flippot,
  • Janice Barros-Monteiro,
  • Nicola Segata,
  • Antoine Thiery-Vuillemin,
  • Silvia Formenti,
  • Tatiana Kuznetsova,
  • Bernard Escudier,
  • Lisa Derosa,
  • Laurence Zitvogel,
  • Toni K. Choueiri,
  • Laurence Albiges

摘要

Patients with metastatic renal cell carcinoma treated with immune checkpoint inhibitors or antiangiogenic tyrosine kinase inhibitors may develop resistance driven by gut dysbiosis, which disrupts the MAdCAM-1–α4β7 axis and promotes the recruitment of immunosuppressive IL-17-producing T regulatory (Tr17) cells into tumors. We evaluated soluble MAdCAM-1 (sMAdCAM-1) as a prognostic biomarker in 1,051 patients from three cohorts: JAVELIN Renal 101 (avelumab plus axitinib versus sunitinib), SURF (sunitinib) and NIVOREN (nivolumab after tyrosine kinase inhibitors). In the JAVELIN cohort, baseline sMAdCAM-1 levels >180 ng ml−1 were associated with significantly improved progression-free survival (13.9 versus 8.4 months, P < 0.01) and overall survival (18 months: 84.2% versus 68.1%, P < 0.01), independent of IMDC risk groups. We validated the prognostic value of sMAdCAM-1 for overall survival in the SURF and NIVOREN cohorts. Notably, low sMAdCAM-1 levels were associated with an immunosuppressive gut microbiota profile dominated by Enterocloster species. Therefore, sMAdCAM-1 deserves further investigations as a biomarker-guided tool for microbiota-targeted interventions.