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Interplay of somatic alterations and immune infiltration modulates response to PD-1 blockade in advanced clear cell renal cell carcinoma -- CA209-009

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
EGAS00001004290 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
EGAF00003476791 fastq.gz 2.1 GB
EGAF00003476792 fastq.gz 2.1 GB
EGAF00003476793 fastq.gz 1.1 GB
EGAF00003476794 fastq.gz 1.1 GB
EGAF00003476795 fastq.gz 1.2 GB
EGAF00003476796 fastq.gz 1.1 GB
EGAF00003477353 fastq.gz 3.9 GB
EGAF00003477354 fastq.gz 4.1 GB
EGAF00003477355 fastq.gz 8.4 GB
EGAF00003477356 fastq.gz 10.0 GB
EGAF00003477357 fastq.gz 3.1 GB
EGAF00003477358 fastq.gz 3.6 GB
EGAF00003477359 fastq.gz 3.9 GB
EGAF00003477360 fastq.gz 4.2 GB
EGAF00003477361 fastq.gz 6.7 GB
EGAF00003477362 fastq.gz 7.6 GB
EGAF00003477363 fastq.gz 6.9 GB
EGAF00003477364 fastq.gz 7.4 GB
EGAF00003477365 fastq.gz 10.1 GB
EGAF00003477366 fastq.gz 11.1 GB
EGAF00003477367 fastq.gz 3.8 GB
EGAF00003477368 fastq.gz 4.1 GB
EGAF00003477369 fastq.gz 7.0 GB
EGAF00003477370 fastq.gz 8.1 GB
EGAF00003477371 fastq.gz 14.1 GB
EGAF00003477372 fastq.gz 16.4 GB
EGAF00003477373 fastq.gz 7.7 GB
EGAF00003477374 fastq.gz 8.4 GB
EGAF00003477375 fastq.gz 3.1 GB
EGAF00003477376 fastq.gz 3.4 GB
EGAF00003477377 fastq.gz 6.2 GB
EGAF00003477378 fastq.gz 7.0 GB
EGAF00003477379 fastq.gz 6.9 GB
EGAF00003477380 fastq.gz 7.7 GB
EGAF00003477381 fastq.gz 3.4 GB
EGAF00003477382 fastq.gz 3.7 GB
EGAF00003477383 fastq.gz 2.9 GB
EGAF00003477384 fastq.gz 3.4 GB
EGAF00003477385 fastq.gz 9.6 GB
EGAF00003477386 fastq.gz 10.1 GB
EGAF00003477387 fastq.gz 3.8 GB
EGAF00003477388 fastq.gz 4.2 GB
EGAF00003477389 fastq.gz 3.9 GB
EGAF00003477390 fastq.gz 4.1 GB
EGAF00003477391 fastq.gz 3.3 GB
EGAF00003477392 fastq.gz 3.5 GB
EGAF00003477393 fastq.gz 3.3 GB
EGAF00003477394 fastq.gz 3.6 GB
EGAF00003477395 fastq.gz 22.5 GB
EGAF00003477396 fastq.gz 25.4 GB
EGAF00003477397 fastq.gz 3.6 GB
EGAF00003477398 fastq.gz 3.9 GB
EGAF00003477399 fastq.gz 7.1 GB
EGAF00003477400 fastq.gz 8.4 GB
EGAF00003477401 fastq.gz 5.6 GB
EGAF00003477402 fastq.gz 6.5 GB
EGAF00003477403 fastq.gz 8.0 GB
EGAF00003477404 fastq.gz 8.5 GB
EGAF00003477405 fastq.gz 3.3 GB
EGAF00003477406 fastq.gz 3.5 GB
EGAF00003477407 fastq.gz 14.1 GB
EGAF00003477408 fastq.gz 14.6 GB
62 Files (401.3 GB)