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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.

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Studies are experimental investigations of a particular phenomenon, e.g., case-control studies on a particular trait or cancer research projects reporting matching cancer normal genomes from patients.

Study ID Study Title Study Type
EGAS00001004291 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 Located in
EGAF00003476420 fastq.gz 1.3 GB
EGAF00003476421 fastq.gz 1.3 GB
EGAF00003476422 fastq.gz 1.1 GB
EGAF00003476423 fastq.gz 1.1 GB
EGAF00003476424 fastq.gz 843.7 MB
EGAF00003476425 fastq.gz 828.5 MB
EGAF00003476426 fastq.gz 1.6 GB
EGAF00003476427 fastq.gz 1.6 GB
EGAF00003476428 fastq.gz 809.8 MB
EGAF00003476429 fastq.gz 788.9 MB
EGAF00003476430 fastq.gz 3.7 GB
EGAF00003476431 fastq.gz 4.0 GB
EGAF00003476432 fastq.gz 169.1 MB
EGAF00003476433 fastq.gz 159.2 MB
EGAF00003476434 fastq.gz 1.3 GB
EGAF00003476435 fastq.gz 1.3 GB
EGAF00003476436 fastq.gz 826.6 MB
EGAF00003476437 fastq.gz 850.8 MB
EGAF00003476438 fastq.gz 1.2 GB
EGAF00003476439 fastq.gz 1.2 GB
EGAF00003476440 fastq.gz 711.0 MB
EGAF00003476441 fastq.gz 651.8 MB
EGAF00003476442 fastq.gz 1.4 GB
EGAF00003476443 fastq.gz 1.4 GB
EGAF00003476444 fastq.gz 2.0 GB
EGAF00003476445 fastq.gz 2.1 GB
EGAF00003476446 fastq.gz 1.1 GB
EGAF00003476447 fastq.gz 1.1 GB
EGAF00003476448 fastq.gz 490.4 MB
EGAF00003476449 fastq.gz 483.0 MB
EGAF00003476450 fastq.gz 804.8 MB
EGAF00003476451 fastq.gz 824.6 MB
EGAF00003476452 fastq.gz 1.4 GB
EGAF00003476453 fastq.gz 1.5 GB
EGAF00003476454 fastq.gz 2.3 GB
EGAF00003476455 fastq.gz 2.5 GB
EGAF00003476456 fastq.gz 715.9 MB
EGAF00003476457 fastq.gz 701.3 MB
EGAF00003476458 fastq.gz 4.0 GB
EGAF00003476459 fastq.gz 4.6 GB
EGAF00003476460 fastq.gz 3.6 GB
EGAF00003476461 fastq.gz 4.0 GB
EGAF00003476462 fastq.gz 5.2 GB
EGAF00003476463 fastq.gz 5.9 GB
EGAF00003476464 fastq.gz 7.4 GB
EGAF00003476465 fastq.gz 8.7 GB
EGAF00003476466 fastq.gz 10.6 GB
EGAF00003476467 fastq.gz 12.2 GB
EGAF00003476468 fastq.gz 3.3 GB
EGAF00003476469 fastq.gz 3.9 GB
EGAF00003476470 fastq.gz 4.1 GB
EGAF00003476471 fastq.gz 4.4 GB
EGAF00003476472 fastq.gz 2.8 GB
EGAF00003476473 fastq.gz 3.1 GB
EGAF00003476474 fastq.gz 2.9 GB
EGAF00003476475 fastq.gz 3.2 GB
EGAF00003476476 fastq.gz 8.9 GB
EGAF00003476477 fastq.gz 10.1 GB
EGAF00003476478 fastq.gz 4.5 GB
EGAF00003476479 fastq.gz 5.1 GB
EGAF00003476480 fastq.gz 2.2 GB
EGAF00003476481 fastq.gz 2.4 GB
EGAF00003476482 fastq.gz 3.5 GB
EGAF00003476483 fastq.gz 3.7 GB
EGAF00003476484 fastq.gz 7.5 GB
EGAF00003476485 fastq.gz 8.7 GB
EGAF00003476486 fastq.gz 4.3 GB
EGAF00003476487 fastq.gz 5.0 GB
EGAF00003476488 fastq.gz 3.9 GB
EGAF00003476489 fastq.gz 4.5 GB
EGAF00003476490 fastq.gz 2.9 GB
EGAF00003476491 fastq.gz 3.3 GB
EGAF00003476492 fastq.gz 5.2 GB
EGAF00003476493 fastq.gz 5.7 GB
EGAF00003476494 fastq.gz 3.7 GB
EGAF00003476495 fastq.gz 4.1 GB
EGAF00003476496 fastq.gz 8.2 GB
EGAF00003476497 fastq.gz 9.5 GB
EGAF00003476498 fastq.gz 4.0 GB
EGAF00003476499 fastq.gz 4.7 GB
EGAF00003476500 fastq.gz 4.1 GB
EGAF00003476501 fastq.gz 4.6 GB
EGAF00003476502 fastq.gz 4.7 GB
EGAF00003476503 fastq.gz 5.3 GB
EGAF00003476504 fastq.gz 12.4 GB
EGAF00003476505 fastq.gz 14.3 GB
EGAF00003476506 fastq.gz 7.5 GB
EGAF00003476507 fastq.gz 8.0 GB
EGAF00003476508 fastq.gz 3.6 GB
EGAF00003476509 fastq.gz 4.1 GB
EGAF00003476510 fastq.gz 3.0 GB
EGAF00003476511 fastq.gz 3.4 GB
EGAF00003476512 fastq.gz 4.7 GB
EGAF00003476513 fastq.gz 5.4 GB
EGAF00003476514 fastq.gz 9.3 GB
EGAF00003476515 fastq.gz 10.4 GB
EGAF00003476516 fastq.gz 3.1 GB
EGAF00003476517 fastq.gz 3.4 GB
EGAF00003476518 fastq.gz 6.4 GB
EGAF00003476519 fastq.gz 7.7 GB
EGAF00003476520 fastq.gz 3.3 GB
EGAF00003476521 fastq.gz 3.8 GB
EGAF00003476522 fastq.gz 5.3 GB
EGAF00003476523 fastq.gz 5.9 GB
EGAF00003476524 fastq.gz 3.1 GB
EGAF00003476525 fastq.gz 3.4 GB
106 Files (417.8 GB)