Soluble MAdCAM-1 as a biomarker in metastatic renal cell carcinoma: analysis of three studies

Patients with metastatic renal cell carcinoma (mRCC) treated with immune checkpoint inhibitors or antiangiogenic TKIs 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 cells into tumors. Pooled analysis of 1051 participants of JAVELIN Renal 101 (avelumab plus axitinib versus sunitinib), SURF (sunitinib), and NIVOREN (nivolumab after TKIs) evaluated soluble MAdCAM-1 (sMAdCAM-1) as prognostic biomarker. In the JAVELIN Renal 101 trial (training cohort), baseline sMAdCAM-1 levels ≥ 180 ng/ml were associated with significantly improved survival outcomes, independent of IMDC risk groups. The prognostic value of sMAdCAM-1 for overall survival was validated in the SURF and NIVOREN cohorts. The authors conclude that sMAdCAM-1 deserves further investigation as a biomarker for microbiota-targeted interventions.