Interplay of somatic alterations and immune infiltration modulates response to PD-1 blockade in advanced clear cell renal cell carcinoma -- CA209-010

Immune checkpoint inhibitors targeting the PD-1 pathway have transformed the management of many advanced malignancies, including clear cell renal cell carcinoma (ccRCC), but the drivers and resistors of PD-1 response remain incompletely elucidated. Here, we analyzed 592 tumors collected from advanced ccRCC patients enrolled in prospective clinical trials of treatment with PD-1 blockade (or mTOR inhibition as control arm) by whole-exome and RNA-sequencing, integrated with immunofluorescence analysis, to define the somatic alteration landscape of late-stage ccRCC and to uncover the immunogenomic determinants of therapeutic response. While conventional genomic markers (tumor mutation burden, neoantigen load) and degree of CD8+ T cell infiltration were not associated with clinical response, we discovered numerous chromosomal alterations in advanced ccRCC associated with response or resistance to PD-1 blockade. These advanced tumors were highly CD8+ T cell infiltrated, with only 22% and 5% with an immune desert and immune excluded phenotype, respectively. Our analysis revealed that CD8+ infiltrated tumors are depleted of favorable PBRM1 mutations and are enriched for unfavorable chromosomal losses of 9p21.3 when compared to non-infiltrated tumors. These data demonstrate how the interplay of somatic alterations and immunophenotypes impacts therapeutic efficacy.

06/03/2020
53 samples
DAC: EGAC00001001519
Technology: Illumina HiSeq 2500

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Study ID	Study Title	Study Type
EGAS00001004291	Interplay of somatic alterations and immune infiltration modulates response to PD-1 blockade in advanced clear cell RCC -- CA209-010	Other

This table displays only public information pertaining to the files in the dataset. If you wish to access this dataset, please submit a request. If you already have access to these data files, please consult the download documentation.

ID	File Type	Size	Quality Report
EGAF00003476420	fastq.gz	1.3 GB	Report
EGAF00003476421	fastq.gz	1.3 GB	Report
EGAF00003476422	fastq.gz	1.1 GB	Report
EGAF00003476423	fastq.gz	1.1 GB	Report
EGAF00003476424	fastq.gz	843.7 MB	Report
EGAF00003476425	fastq.gz	828.5 MB	Report
EGAF00003476426	fastq.gz	1.6 GB	Report
EGAF00003476427	fastq.gz	1.6 GB	Report
EGAF00003476428	fastq.gz	809.8 MB	Report
EGAF00003476429	fastq.gz	788.9 MB	Report
EGAF00003476430	fastq.gz	3.7 GB	Report
EGAF00003476431	fastq.gz	4.0 GB	Report
EGAF00003476432	fastq.gz	169.1 MB	Report
EGAF00003476433	fastq.gz	159.2 MB	Report
EGAF00003476434	fastq.gz	1.3 GB	Report
EGAF00003476435	fastq.gz	1.3 GB	Report
EGAF00003476436	fastq.gz	826.6 MB	Report
EGAF00003476437	fastq.gz	850.8 MB	Report
EGAF00003476438	fastq.gz	1.2 GB	Report
EGAF00003476439	fastq.gz	1.2 GB	Report
EGAF00003476440	fastq.gz	711.0 MB	Report
EGAF00003476441	fastq.gz	651.8 MB	Report
EGAF00003476442	fastq.gz	1.4 GB	Report
EGAF00003476443	fastq.gz	1.4 GB	Report
EGAF00003476444	fastq.gz	2.0 GB	Report
EGAF00003476445	fastq.gz	2.1 GB	Report
EGAF00003476446	fastq.gz	1.1 GB	Report
EGAF00003476447	fastq.gz	1.1 GB	Report
EGAF00003476448	fastq.gz	490.4 MB	Report
EGAF00003476449	fastq.gz	483.0 MB	Report
EGAF00003476450	fastq.gz	804.8 MB	Report
EGAF00003476451	fastq.gz	824.6 MB	Report
EGAF00003476452	fastq.gz	1.4 GB	Report
EGAF00003476453	fastq.gz	1.5 GB	Report
EGAF00003476454	fastq.gz	2.3 GB	Report
EGAF00003476455	fastq.gz	2.5 GB	Report
EGAF00003476456	fastq.gz	715.9 MB	Report
EGAF00003476457	fastq.gz	701.3 MB	Report
EGAF00003476458	fastq.gz	4.0 GB	Report
EGAF00003476459	fastq.gz	4.6 GB	Report
EGAF00003476460	fastq.gz	3.6 GB	Report
EGAF00003476461	fastq.gz	4.0 GB	Report
EGAF00003476462	fastq.gz	5.2 GB	Report
EGAF00003476463	fastq.gz	5.9 GB	Report
EGAF00003476464	fastq.gz	7.4 GB	Report
EGAF00003476465	fastq.gz	8.7 GB	Report
EGAF00003476466	fastq.gz	10.6 GB	Report
EGAF00003476467	fastq.gz	12.2 GB	Report
EGAF00003476468	fastq.gz	3.3 GB	Report
EGAF00003476469	fastq.gz	3.9 GB	Report
EGAF00003476470	fastq.gz	4.1 GB	Report
EGAF00003476471	fastq.gz	4.4 GB	Report
EGAF00003476472	fastq.gz	2.8 GB	Report
EGAF00003476473	fastq.gz	3.1 GB	Report
EGAF00003476474	fastq.gz	2.9 GB	Report
EGAF00003476475	fastq.gz	3.2 GB	Report
EGAF00003476476	fastq.gz	8.9 GB	Report
EGAF00003476477	fastq.gz	10.1 GB	Report
EGAF00003476478	fastq.gz	4.5 GB	Report
EGAF00003476479	fastq.gz	5.1 GB	Report
EGAF00003476480	fastq.gz	2.2 GB
EGAF00003476481	fastq.gz	2.4 GB
EGAF00003476482	fastq.gz	3.5 GB	Report
EGAF00003476483	fastq.gz	3.7 GB	Report
EGAF00003476484	fastq.gz	7.5 GB	Report
EGAF00003476485	fastq.gz	8.7 GB	Report
EGAF00003476486	fastq.gz	4.3 GB	Report
EGAF00003476487	fastq.gz	5.0 GB	Report
EGAF00003476488	fastq.gz	3.9 GB	Report
EGAF00003476489	fastq.gz	4.5 GB	Report
EGAF00003476490	fastq.gz	2.9 GB	Report
EGAF00003476491	fastq.gz	3.3 GB	Report
EGAF00003476492	fastq.gz	5.2 GB	Report
EGAF00003476493	fastq.gz	5.7 GB	Report
EGAF00003476494	fastq.gz	3.7 GB	Report
EGAF00003476495	fastq.gz	4.1 GB	Report
EGAF00003476496	fastq.gz	8.2 GB	Report
EGAF00003476497	fastq.gz	9.5 GB	Report
EGAF00003476498	fastq.gz	4.0 GB	Report
EGAF00003476499	fastq.gz	4.7 GB	Report
EGAF00003476500	fastq.gz	4.1 GB	Report
EGAF00003476501	fastq.gz	4.6 GB	Report
EGAF00003476502	fastq.gz	4.7 GB	Report
EGAF00003476503	fastq.gz	5.3 GB	Report
EGAF00003476504	fastq.gz	12.4 GB	Report
EGAF00003476505	fastq.gz	14.3 GB	Report
EGAF00003476506	fastq.gz	7.5 GB	Report
EGAF00003476507	fastq.gz	8.0 GB	Report
EGAF00003476508	fastq.gz	3.6 GB	Report
EGAF00003476509	fastq.gz	4.1 GB	Report
EGAF00003476510	fastq.gz	3.0 GB	Report
EGAF00003476511	fastq.gz	3.4 GB	Report
EGAF00003476512	fastq.gz	4.7 GB	Report
EGAF00003476513	fastq.gz	5.4 GB	Report
EGAF00003476514	fastq.gz	9.3 GB	Report
EGAF00003476515	fastq.gz	10.4 GB	Report
EGAF00003476516	fastq.gz	3.1 GB	Report
EGAF00003476517	fastq.gz	3.4 GB	Report
EGAF00003476518	fastq.gz	6.4 GB	Report
EGAF00003476519	fastq.gz	7.7 GB	Report
EGAF00003476520	fastq.gz	3.3 GB	Report
EGAF00003476521	fastq.gz	3.8 GB	Report
EGAF00003476522	fastq.gz	5.3 GB	Report
EGAF00003476523	fastq.gz	5.9 GB	Report
EGAF00003476524	fastq.gz	3.1 GB	Report
EGAF00003476525	fastq.gz	3.4 GB	Report
106 Files (417.8 GB)