2022
DOI: 10.1007/s00262-022-03346-7
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BAP1 and PTEN mutations shape the immunological landscape of clear cell renal cell carcinoma and reveal the intertumoral heterogeneity of T cell suppression: a proof-of-concept study

Abstract: Clear cell renal cell carcinoma (ccRCC) is an immunologically vulnerable tumor entity, and immune checkpoint inhibitors are now widely used to treat patients with advanced disease. Whether and to what extent immune responses in ccRCC are shaped by genetic alterations, however, is only beginning to emerge. In this proof-of-concept study, we performed a detailed correlative analysis of the mutational and immunological landscapes in a series of 23 consecutive kidney cancer patients. We discovered that a high infi… Show more

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Cited by 10 publications
(7 citation statements)
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“…Mutations in BAP1 , which were the most frequent in CCRCC among all cancers ( Figure 3A ), were suggested to be pathogenic and promote CD8 + T cell infiltration in CCRCC. 37 In our data, BAP1 mutation correlated with the downregulation of cognate RNA and protein expression in CCRCC ( Figures 3C , S3A , and S3B ). This is consistent with the previous observation that decreased BAP1 expression results in higher infiltration of immune cells.…”
Section: Resultssupporting
confidence: 60%
“…Mutations in BAP1 , which were the most frequent in CCRCC among all cancers ( Figure 3A ), were suggested to be pathogenic and promote CD8 + T cell infiltration in CCRCC. 37 In our data, BAP1 mutation correlated with the downregulation of cognate RNA and protein expression in CCRCC ( Figures 3C , S3A , and S3B ). This is consistent with the previous observation that decreased BAP1 expression results in higher infiltration of immune cells.…”
Section: Resultssupporting
confidence: 60%
“…The targeted NGS of tumor tissue from selected patients was performed using the TruSight Oncology 500 panel (Illumina, San Diego, CA, USA), as previously described [20,21].…”
Section: Targeted Next Generation Sequencing (Ngs)mentioning
confidence: 99%
“…In both studies, BAP1 loss of function was associated with a shorter PFS in patients treated with antiangiogenic drugs [37]. When it comes to immunotherapy, there is much preclinical evidence that BAP1 is associated with an immunosuppressive microenvironment: it has been demonstrated that BAP1 mutation is associated with T-cell suppression in preclinical RCC models [52]. Clinical data on BAP1 as a predictor of response to immunotherapy have only recently been published.…”
Section: Bap1mentioning
confidence: 99%