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Combined tumor and immune signals from genomes or transcriptomes predict outcomes of checkpoint inhibition in melanoma.
Freeman, Samuel S; Sade-Feldman, Moshe; Kim, Jaegil; Stewart, Chip; Gonye, Anna L K; Ravi, Arvind; Arniella, Monica B; Gushterova, Irena; LaSalle, Thomas J; Blaum, Emily M; Yizhak, Keren; Frederick, Dennie T; Sharova, Tatyana; Leshchiner, Ignaty; Elagina, Liudmila; Spiro, Oliver G; Livitz, Dimitri; Rosebrock, Daniel; Aguet, François; Carrot-Zhang, Jian; Ha, Gavin; Lin, Ziao; Chen, Jonathan H; Barzily-Rokni, Michal; Hammond, Marc R; Vitzthum von Eckstaedt, Hans C; Blackmon, Shauna M; Jiao, Yunxin J; Gabriel, Stacey; Lawrence, Donald P; Duncan, Lyn M; Stemmer-Rachamimov, Anat O; Wargo, Jennifer A; Flaherty, Keith T; Sullivan, Ryan J; Boland, Genevieve M; Meyerson, Matthew; Getz, Gad; Hacohen, Nir.
Afiliação
  • Freeman SS; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Sade-Feldman M; Department of Biomedical Informatics, Harvard Medical School, Boston, MA 02115, USA.
  • Kim J; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Stewart C; Department of Medicine, Center for Cancer Research, Massachusetts General Hospital, Boston, MA 02114, USA.
  • Gonye ALK; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Ravi A; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Arniella MB; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Gushterova I; Department of Medicine, Center for Cancer Research, Massachusetts General Hospital, Boston, MA 02114, USA.
  • LaSalle TJ; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Blaum EM; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
  • Yizhak K; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Frederick DT; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Sharova T; Department of Medicine, Center for Cancer Research, Massachusetts General Hospital, Boston, MA 02114, USA.
  • Leshchiner I; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Elagina L; Department of Medicine, Center for Cancer Research, Massachusetts General Hospital, Boston, MA 02114, USA.
  • Spiro OG; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Livitz D; Department of Medicine, Center for Cancer Research, Massachusetts General Hospital, Boston, MA 02114, USA.
  • Rosebrock D; Department of Cell Biology and Cancer Science, Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa 2611001, Israel.
  • Aguet F; Department of Medicine, Center for Cancer Research, Massachusetts General Hospital, Boston, MA 02114, USA.
  • Carrot-Zhang J; Department of Medicine, Center for Cancer Research, Massachusetts General Hospital, Boston, MA 02114, USA.
  • Ha G; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Lin Z; Department of Medicine, Center for Cancer Research, Massachusetts General Hospital, Boston, MA 02114, USA.
  • Chen JH; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Barzily-Rokni M; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Hammond MR; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Vitzthum von Eckstaedt HC; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Blackmon SM; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Jiao YJ; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Gabriel S; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
  • Lawrence DP; Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle 98109, WA, USA.
  • Duncan LM; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Stemmer-Rachamimov AO; Harvard University, Cambridge MA, 02138.
  • Wargo JA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Flaherty KT; Department of Pathology, Massachusetts General Hospital, Boston 02114, MA, USA.
  • Sullivan RJ; Department of Medicine, Center for Cancer Research, Massachusetts General Hospital, Boston, MA 02114, USA.
  • Boland GM; Department of Medicine, Center for Cancer Research, Massachusetts General Hospital, Boston, MA 02114, USA.
  • Meyerson M; Department of Medicine, Center for Cancer Research, Massachusetts General Hospital, Boston, MA 02114, USA.
  • Getz G; Department of Medicine, Center for Cancer Research, Massachusetts General Hospital, Boston, MA 02114, USA.
  • Hacohen N; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Cell Rep Med ; 3(2): 100500, 2022 02 15.
Article em En | MEDLINE | ID: mdl-35243413
ABSTRACT
Immune checkpoint blockade (CPB) improves melanoma outcomes, but many patients still do not respond. Tumor mutational burden (TMB) and tumor-infiltrating T cells are associated with response, and integrative models improve survival prediction. However, integrating immune/tumor-intrinsic features using data from a single assay (DNA/RNA) remains underexplored. Here, we analyze whole-exome and bulk RNA sequencing of tumors from new and published cohorts of 189 and 178 patients with melanoma receiving CPB, respectively. Using DNA, we calculate T cell and B cell burdens (TCB/BCB) from rearranged TCR/Ig sequences and find that patients with TMBhigh and TCBhigh or BCBhigh have improved outcomes compared to other patients. By combining pairs of immune- and tumor-expressed genes, we identify three gene pairs associated with response and survival, which validate in independent cohorts. The top model includes lymphocyte-expressed MAP4K1 and tumor-expressed TBX3. Overall, RNA or DNA-based models combining immune and tumor measures improve predictions of melanoma CPB outcomes.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Transcriptoma / Melanoma Tipo de estudo: Prognostic_studies / Risk_factors_studies Limite: Humans Idioma: En Revista: Cell Rep Med Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Transcriptoma / Melanoma Tipo de estudo: Prognostic_studies / Risk_factors_studies Limite: Humans Idioma: En Revista: Cell Rep Med Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Estados Unidos