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Nat Commun. 2016 Aug 30;7:12624. doi: 10.1038/ncomms12624.

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

Author information

Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, USA.
GI Oncology Research, Drug Development Unit, Sarah Cannon Research Institute, 250 25th Avenue North, Suite 100, Nashville, Tennessee, 37203, USA.
Department of Internal Medicine and Melanoma Unit, Yale Cancer Center, New Haven, Connecticut 06511, USA.
Roche Diagnostics GmbH, Nonnenwald 2, 82377 Penzberg, Germany.
Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, Massachusets 02215, USA.
Dana-Farber/Brigham and Women's Cancer Center, 450 Brookline Avenue, Boston, Massachusets 02215, USA.


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.

[Indexed for MEDLINE]
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Conflict of interest statement

This study was sponsored by Genentech, Inc., a member of the Roche Group, which provided the study drug. Some of the authors of this manuscript are employees of Genentech/Roche. The remaining authors declare no competing financial interests.

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