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We use cellular-resolution spatial transcriptomics in patients with immunotherapy na\u00efve and exposed primary ccRCC tumors to better understand immunotherapy resistance.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Spatial molecular imaging of tumor and adjacent stroma samples from 21 tumors suggests that viable tumors following immunotherapy harbor more stromal CD8\u2009+\u2009T cells and neutrophils than immunotherapy na\u00efve tumors.\n                      <jats:italic>YES1<\/jats:italic>\n                      is significantly upregulated in immunotherapy exposed tumor cells. Spatial GSEA shows that the epithelial-mesenchymal transition pathway is spatially enriched and the associated ligand-receptor transcript pair\n                      <jats:italic>COL4A1<\/jats:italic>\n                      -\n                      <jats:italic>ITGAV<\/jats:italic>\n                      has significantly higher autocorrelation in the stroma after exposure to immunotherapy. More integrin \u03b1V\u2009+\u2009cells are observed in immunotherapy exposed stroma on multiplex immunofluorescence validation. Compared to other cancers in TCGA, ccRCC tumors have the highest expression of both\n                      <jats:italic>COL4A1<\/jats:italic>\n                      and\n                      <jats:italic>ITGAV<\/jats:italic>\n                      . Assessing bulk RNA expression and proteomic correlates in CPTAC databases reveals that collagen IV protein is more abundant in advanced stages of disease.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Spatial transcriptomics of samples of 3 patient cohorts with cRCC tumors indicates that COL4A1 and ITGAV are more autocorrelated in immunotherapy-exposed stroma compared to immunotherapy-na\u00efve tumors, with high expression among fibroblasts, tumor cells, and endothelium. Further research is needed to understand changes in the ccRCC tumor immune microenvironment and explore potential therapeutic role of integrin after immunotherapy treatment.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13059-024-03435-z","type":"journal-article","created":{"date-parts":[[2024,12,5]],"date-time":"2024-12-05T07:18:20Z","timestamp":1733383100000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Increased spatial coupling of integrin and collagen IV in the immunoresistant clear-cell renal-cell carcinoma tumor microenvironment"],"prefix":"10.1186","volume":"25","author":[{"given":"Alex C.","family":"Soupir","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitchell T.","family":"Hayes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taylor C.","family":"Peak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oscar","family":"Ospina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas H.","family":"Chakiryan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anders E.","family":"Berglund","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul A.","family":"Stewart","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Nguyen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos Moran","family":"Segura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natasha L.","family":"Francis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola M. 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All experimental methods comply with the Declaration of Helsinki for Medical Research involving Human Subjects.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The corresponding author certifies that all conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript (i.e., employment\/affiliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patents filed, received, or pending), are the following: ACS, MTH, TCP, OEO, NHC, AEB, PAS, JN, CMS, NLF, PMRE, KYT, JAB, YCP, JD, LAM, WEG, and BLF have no relevant disclosures; BJM is an NCCN Kidney Cancer Panel Member and an advisor for Merck; RL received research support from Predicine, Veracyte, CG Oncology, Valar Labs, and Merck, is on the clinical trials committee for CG Oncology, is scientific advisor for Bristol Myers Squibb, Merck, Fergene, Arquer Diagnostics, Urogen Pharma, Lucence, CG Oncology, and Janssen, and has received honoraria from SAI MedPartners, Solstice Health Communications, Putnam Associates, and UroToday; JJM is Associate Center Director at Moffitt Cancer Center, has ownership interest in Aleta Biotherapeutics, CG Oncology, Turnstone Biologics, Ankyra Therapeutics, and AffyImmune Therapeutics, and is a paid consultant\/paid advisory board member for ONCoPEP, CG Oncology, Turnstone Biologics, Vault Pharma, Ankyra Therapeutics, AffyImmune Therapeutics, UbiVac, Vycellix, and Aleta Biotherapeutics; NS, SK, and MG are or formerly were employees of NanoString.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"308"}}