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Clinical activity and molecular correlates of response to atezolizumab alone or in combination with bevacizumab versus sunitinib in renal cell carcinoma

We examined pre-treatment tumors from participants of the IMmotion150 trial. Biomarker analyses indicate that high angiogenesis gene expression was associated with improved PFS within the sunitinib arm, and high T-effector/IFNγ response (Teff) gene expression with longer PFS in atezolizumab + bevacizumab vs sunitinib patients. In high Teff tumors, concomitant high myeloid inflammation was associated with worse PFS in the atezolizumab monotherapy arm; adding bevacizumab to atezolizumab in this subgroup improved PFS vs atezolizumab. Molecular profiles suggest that prediction of outcomes with VEGF inhibitors and immunotherapy may be possible in mRCC, and bevacizumab may overcome myeloid inflammation-associated atezolizumab resistance.

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Dataset ID Description Technology Samples
EGAD00001004183 Illumina HiSeq 2500 589
Publications Citations
Clinical activity and molecular correlates of response to atezolizumab alone or in combination with bevacizumab versus sunitinib in renal cell carcinoma.
Nat Med 24: 2018 749-757
546
PBRM1 loss defines a nonimmunogenic tumor phenotype associated with checkpoint inhibitor resistance in renal carcinoma.
Nat Commun 11: 2020 2135
86
Escape from nonsense-mediated decay associates with anti-tumor immunogenicity.
Nat Commun 11: 2020 3800
45
A pan-cancer analysis of PBAF complex mutations and their association with immunotherapy response.
Nat Commun 11: 2020 4168
27
Antagonistic Inflammatory Phenotypes Dictate Tumor Fate and Response to Immune Checkpoint Blockade.
Immunity 53: 2020 1215-1229.e8
96
Replication stress response defects are associated with response to immune checkpoint blockade in nonhypermutated cancers.
Sci Transl Med 13: 2021 eabe6201
15
PBRM1 Inactivation Promotes Upregulation of Human Endogenous Retroviruses in a HIF-Dependent Manner.
Cancer Immunol Res 10: 2022 285-290
8
Decoding the multicellular ecosystem of vena caval tumor thrombus in clear cell renal cell carcinoma by single-cell RNA sequencing.
Genome Biol 23: 2022 87
19
Transcriptomic datasets of cancer patients treated with immune-checkpoint inhibitors: a systematic review.
J Transl Med 20: 2022 249
21
The cuproptosis-associated 13 gene signature as a robust predictor for outcome and response to immune- and targeted-therapies in clear cell renal cell carcinoma.
Front Immunol 13: 2022 971142
16
Tumor and immune remodeling following radiotherapy in human renal cell carcinoma.
J Immunother Cancer 11: 2023 e006392
1
Dyskerin and telomerase RNA component are sex-differentially associated with outcomes and Sunitinib response in patients with clear cell renal cell carcinoma.
Biol Sex Differ 14: 2023 46
0
Intratumoral T-cell and B-cell receptor architecture associates with distinct immune tumor microenvironment features and clinical outcomes of anti-PD-1/L1 immunotherapy.
J Immunother Cancer 11: 2023 e006941
1
Multiple instance learning to predict immune checkpoint blockade efficacy using neoantigen candidates.
iScience 26: 2023 108014
0