Integrative Molecular Characterization of Sarcomatoid and Rhabdoid Renal Cell Carcinoma Reveals Determinants of Poor Prognosis and Response to Immune Checkpoint Inhibitors
Integrative Molecular Characterization of Sarcomatoid and Rhabdoid Renal Cell Carcinoma Reveals Determinants of Poor Prognosis and Response to Immune Checkpoint Inhibitors
Abstract Sarcomatoid and rhabdoid (S/R) renal cell carcinoma (RCC) are highly aggressive tumors with limited molecular and clinical characterization. Emerging evidence suggests immune checkpoint inhibitors (ICI) are particularly effective for these tumors1–3, although the biological basis for this property is largely unknown. Here, we evaluate multiple clinical trial and real-world cohorts of S/R RCC to characterize their molecular features, clinical outcomes, and immunologic characteristics. We find that S/R RCC tumors harbor distinctive molecular features that may account for their aggressive behavior, including BAP1 mutations, CDKN2A deletions, and increased expression of MYC transcriptional programs. We show that these tumors are highly responsive to ICI and that they exhibit an immune-inflamed phenotype characterized by immune activation, increased cytotoxic immune infiltration, upregulation of antigen presentation machinery genes, and PD-L1 expression. Our findings shed light on the molecular drivers of aggressivity and responsiveness to immune checkpoint inhibitors of S/R RCC tumors.
Wind-Rotolo Megan、Van Allen Eliezer M.、Camp Sabrina、Linehan W. Marston、Signoretti Sabina、Braun David A.、Pan Wenting、Gao Xin、Flaifel Abdallah、Ellis Leigh、Freedman Matthew L.、He Meng Xiao、Bouchard Gabrielle、Nuzzo Pier Vitale、Ficial Miriam、Sticco-Ivins Maura、Hirsch Laure、Sun Maxine、Alaiwi Sarah Abou、Hirsch Michelle S.、Chang Steven L.、Flippot Ronan、Nyman Jackson、Heng Daniel Y.C.、Bakouny Ziad、McDermott David F.、Ho Thai H.、Xie Wanling、Genovese Giannicola、Vokes Natalie、McGregor Bradley A.、Bosma-Moody Alice、Pomerantz Mark、Ross-Macdonald Petra、Harshman Lauren C.、Tang Stephen、Hou Yue、Choueiri Toni K.、Dudani Shaan、Wu Catherine J.、Atkins Michael B.、Lee Gwo-Shu Mary、Shukla Sachet A.、Wei Xiao X.、Viswanathan Srinivas R.、Berchuck Jacob E.、Sant?ˉAngelo Miriam、Steinharter John A.、Forman Juliet、Park Jihye、Nassar Amin H.、Bi Kevin
Bristol-Myers SquibbDepartment of Medical Oncology, Dana-Farber Cancer InstituteDepartment of Medical Oncology, Dana-Farber Cancer InstituteUrologic Oncology Branch, Center for Cancer Research, National Cancer InstituteDepartment of Pathology, Brigham and Women?ˉs Hospital||Department of Oncologic Pathology, Dana-Farber Cancer InstituteDepartment of Medical Oncology, Dana-Farber Cancer InstituteDepartment of Medical Oncology, Dana-Farber Cancer InstituteDepartment of Medicine, Massachusetts General Hospital Cancer CenterDepartment of Pathology, Brigham and Women?ˉs HospitalDepartment of Pathology, Brigham and Women?ˉs Hospital||Department of Oncologic Pathology, Dana-Farber Cancer InstituteDepartment of Medical Oncology, Dana-Farber Cancer InstituteDepartment of Medical Oncology, Dana-Farber Cancer InstituteDepartment of Medical Oncology, Dana-Farber Cancer InstituteDepartment of Medical Oncology, Dana-Farber Cancer InstituteDepartment of Pathology, Brigham and Women?ˉs HospitalDepartment of Pathology, Brigham and Women?ˉs HospitalDepartment of Medical Oncology, Dana-Farber Cancer InstituteDepartment of Medical Oncology, Dana-Farber Cancer InstituteDepartment of Medical Oncology, Dana-Farber Cancer InstituteDepartment of Pathology, Brigham and Women?ˉs HospitalDepartment of Medical Oncology, Dana-Farber Cancer InstituteDepartment of Medical Oncology, Dana-Farber Cancer InstituteDepartment of Medical Oncology, Dana-Farber Cancer InstituteTom Baker Cancer Centre, University of CalgaryDepartment of Medical Oncology, Dana-Farber Cancer InstituteBeth Israel Deaconess Medical CenterDivision of Hematology and Medical OncologyDepartment of Data Sciences, Dana-Farber Cancer InstituteDepartment of Genomic Medicine, The University of Texas MD Anderson Cancer CenterDepartment of Medical Oncology, Dana-Farber Cancer InstituteDepartment of Medical Oncology, Dana-Farber Cancer InstituteDepartment of Medical Oncology, Dana-Farber Cancer InstituteDepartment of Medical Oncology, Dana-Farber Cancer InstituteBristol-Myers SquibbDepartment of Medical Oncology, Dana-Farber Cancer InstituteDepartment of Medical Oncology, Dana-Farber Cancer InstituteTranslational Immunogenomics Laboratory, Dana-Farber Cancer InstituteDepartment of Medical Oncology, Dana-Farber Cancer InstituteTom Baker Cancer Centre, University of CalgaryDepartment of Medical Oncology, Dana-Farber Cancer Institute||Broad Institute of MIT and HarvardLombardi Comprehensive Cancer Center, Georgetown University Medical CenterDepartment of Medical Oncology, Dana-Farber Cancer InstituteTranslational Immunogenomics Laboratory, Dana-Farber Cancer InstituteDepartment of Medical Oncology, Dana-Farber Cancer InstituteDepartment of Medical Oncology, Dana-Farber Cancer InstituteDepartment of Medical Oncology, Dana-Farber Cancer InstituteDepartment of Pathology, Brigham and Women?ˉs HospitalDepartment of Medical Oncology, Dana-Farber Cancer InstituteDepartment of Medical Oncology, Dana-Farber Cancer Institute||Translational Immunogenomics Laboratory, Dana-Farber Cancer Institute||Lombardi Comprehensive Cancer Center, Georgetown University Medical CenterDepartment of Medical Oncology, Dana-Farber Cancer InstituteDepartment of Medical Oncology, Dana-Farber Cancer InstituteDepartment of Medical Oncology, Dana-Farber Cancer Institute
肿瘤学分子生物学
sarcomatoidrhabdoidrenal cell carcinomaimmune checkpoint inhibitor
Wind-Rotolo Megan,Van Allen Eliezer M.,Camp Sabrina,Linehan W. Marston,Signoretti Sabina,Braun David A.,Pan Wenting,Gao Xin,Flaifel Abdallah,Ellis Leigh,Freedman Matthew L.,He Meng Xiao,Bouchard Gabrielle,Nuzzo Pier Vitale,Ficial Miriam,Sticco-Ivins Maura,Hirsch Laure,Sun Maxine,Alaiwi Sarah Abou,Hirsch Michelle S.,Chang Steven L.,Flippot Ronan,Nyman Jackson,Heng Daniel Y.C.,Bakouny Ziad,McDermott David F.,Ho Thai H.,Xie Wanling,Genovese Giannicola,Vokes Natalie,McGregor Bradley A.,Bosma-Moody Alice,Pomerantz Mark,Ross-Macdonald Petra,Harshman Lauren C.,Tang Stephen,Hou Yue,Choueiri Toni K.,Dudani Shaan,Wu Catherine J.,Atkins Michael B.,Lee Gwo-Shu Mary,Shukla Sachet A.,Wei Xiao X.,Viswanathan Srinivas R.,Berchuck Jacob E.,Sant?ˉAngelo Miriam,Steinharter John A.,Forman Juliet,Park Jihye,Nassar Amin H.,Bi Kevin.Integrative Molecular Characterization of Sarcomatoid and Rhabdoid Renal Cell Carcinoma Reveals Determinants of Poor Prognosis and Response to Immune Checkpoint Inhibitors[EB/OL].(2025-03-28)[2025-06-27].https://www.biorxiv.org/content/10.1101/2020.05.28.121806.点此复制
评论