Atezolizumab in combination with bevacizumab enhances antigen-specific T-cell migration in metastatic renal cell carcinoma

By Jeffrey J. Wallin, Johanna C. Bendell, R. Funke, M. Sznol, Konstanty Korski, S. Jones, G. Hernandez, J. Mier, Xian He, F. Hodi and 12 more. Nature Communications, 2016

648 citations recorded by the source corpus.

Anti-tumour immune activation by checkpoint inhibitors leads to durable responses in a variety of cancers, but combination approaches are required to extend this benefit beyond a subset of patients. In preclinical models tumour-derived VEGF limits immune cell activity while anti-VEGF augments intra-tumoral T-cell infiltration, potentially through vascular normalization and endothelial cell activation. This study investigates how VEGF blockade with bevacizumab could potentiate PD-L1 checkpoint inhibition with atezolizumab in mRCC. Tissue collections are before treatment, after bevacizumab and after the addition of atezolizumab. We discover that intra-tumoral CD8+ T cells increase following combination treatment. A related increase is found in intra-tumoral MHC-I, Th1 and T-effector markers, and chemokines, most notably CX3CL1 (fractalkine). We also discover that the fractalkine receptor increases on peripheral CD8+ T cells with treatment. Furthermore, trafficking lymphocyte increases are observed in tumors following bevacizumab and combination treatment. These data suggest that the anti-VEGF and anti-PD-L1 combination improves antigen-specific T-cell migration. Cancer immunotherapy can be used in combination with other therapies for a better response. Here, the authors conduct a phase Ib clinical study and report the clinical activity and the immune response of the anti-PDL1 agent, atezolizumab, in combination with bevacizumab in ten patients with metastatic renal cell carcinoma.

Subfields: Oncology, Pulmonary and Respiratory Medicine

View Paper: https://www.semanticscholar.org/paper/9f67d318dfbf6b5dbf850c6092edf1798238ee4f

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Citations in the corpus

• Biomarkers for predicting efficacy of PD-1/PD-L1 inhibitors (2018, background): “Patients receiving anti-PD-L1 combined with anti-VEGF therapy exhibited higher response rate than monotherapy [107, 109].”