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Article: Increased spatial coupling of integrin and collagen IV in the immunoresistant clear cell renal cell carcinoma tumor microenvironment.

Soupir, Alex C / Hayes, Mitchell T / Peak, Taylor C / Ospina, Oscar / Chakiryan, Nicholas H / Berglund, Anders E / Stewart, Paul A / Nguyen, Jonathan / Segura, Carlos Moran / Francis, Natasha L / Echevarria, Paola M Ramos / Chahoud, Jad / Li, Roger / Tsai, Kenneth Y / Balasi, Jodi A / Peres, Yamila Caraballo / Dhillon, Jasreman / Martinez, Lindsey A / Gloria, Warren E /
Schurman, Nathan / Kim, Sean / Gregory, Mark / Mulé, James / Fridley, Brooke L / Manley, Brandon J

bioRxiv : the preprint server for biology

2023  

Abstract: Background: Immunotherapy (IO) has improved survival for patients with advanced clear cell renal cell carcinoma (ccRCC), but resistance to therapy develops in most patients. We use cellular-resolution spatial transcriptomics in patients with IO naïve ... ...

Abstract Background: Immunotherapy (IO) has improved survival for patients with advanced clear cell renal cell carcinoma (ccRCC), but resistance to therapy develops in most patients. We use cellular-resolution spatial transcriptomics in patients with IO naïve and IO exposed primary ccRCC tumors to better understand IO resistance. Spatial molecular imaging (SMI) was obtained for tumor and adjacent stroma samples. Spatial gene set enrichment analysis (GSEA) and autocorrelation (coupling with high expression) of ligand-receptor transcript pairs were assessed. Multiplex immunofluorescence (mIF) validation was used for significant autocorrelative findings and the cancer genome atlas (TCGA) and the clinical proteomic tumor analysis consortium (CPTAC) databases were queried to assess bulk RNA expression and proteomic correlates.
Results: 21 patient samples underwent SMI. Viable tumors following IO harbored more stromal CD8+ T cells and neutrophils than IO naïve tumors.
Conclusions: On spatial transcriptomics,
Language English
Publishing date 2023-11-17
Publishing country United States
Document type Preprint
DOI 10.1101/2023.11.16.567457
Database MEDical Literature Analysis and Retrieval System OnLINE

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