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

Baseline sMAdCAM-1 levels greater than 180 ng/ml were associated with significantly improved progression-free survival in the JAVELIN Renal 101 cohort.

• Median progression-free survival was 13.9 months in patients with sMAdCAM-1 >180 ng/ml versus 8.4 months in patients with lower levels.
• The difference was statistically significant (P < 0.01).
• This association was independent of IMDC risk groups.
• The JAVELIN Renal 101 cohort compared avelumab plus axitinib versus sunitinib treatment.

Baseline sMAdCAM-1 levels greater than 180 ng/ml were associated with significantly improved overall survival at 18 months in the JAVELIN Renal 101 cohort.

• Overall survival rate at 18 months was 84.2% in patients with sMAdCAM-1 >180 ng/ml versus 68.1% in patients with lower levels.
• The difference was statistically significant (P < 0.01).
• This association was independent of IMDC risk groups.

The prognostic value of sMAdCAM-1 for overall survival was validated in two additional independent cohorts.

• Validation was performed in the SURF cohort (sunitinib treatment) and the NIVOREN cohort (nivolumab after tyrosine kinase inhibitors).
• The total study population comprised 1,051 patients across all three cohorts.
• sMAdCAM-1 demonstrated prognostic value across different treatment settings including immunotherapy and antiangiogenic therapy.

Low sMAdCAM-1 levels were associated with an immunosuppressive gut microbiota profile dominated by Enterocloster species.

• Patients with low sMAdCAM-1 had a gut microbiota profile characterized by Enterocloster species dominance.
• This microbiota profile is described as immunosuppressive.
• The finding links sMAdCAM-1 as a potential blood-based readout of gut microbiota composition.

Resistance to immune checkpoint inhibitors or antiangiogenic tyrosine kinase inhibitors in metastatic renal cell carcinoma may be driven by gut dysbiosis disrupting the MAdCAM-1-α4β7 axis.

• Disruption of the MAdCAM-1-α4β7 axis promotes recruitment of immunosuppressive IL-17-producing T regulatory (Tr17) cells into tumors.
• This mechanistic rationale provided the basis for evaluating sMAdCAM-1 as a prognostic biomarker.
• The study evaluated both immune checkpoint inhibitor and tyrosine kinase inhibitor treatment contexts.

sMAdCAM-1 was evaluated as a prognostic biomarker across three distinct clinical cohorts encompassing 1,051 patients with metastatic renal cell carcinoma.

• JAVELIN Renal 101 cohort: patients treated with avelumab plus axitinib versus sunitinib.
• SURF cohort: patients treated with sunitinib.
• NIVOREN cohort: patients treated with nivolumab after tyrosine kinase inhibitors.
• Total sample size was 1,051 patients across the three cohorts.