De Mattos-Arruda and Sammut et al. comprehensively analyzed samples from warm autopsies of 10 patients with multiple metastatic breast cancer lesions. Mutations accumulated over time and phylogenetic clustering revealed distinct seeding between metastases, frequently from groups of cellular clones. Most neoantigen-encoding mutations were shared between all or several metastases and were more likely to be expressed than private mutations. HLA loss of heterozygosity likely prevented presentation of half of predicted neoantigens. TME composition was highly heterogeneous and the TCR repertoire appeared to co-evolve with the tumor genome.
To celebrate Cancer Immunotherapy month, our partners at ReFigure created a collection of figures that you can check out at http://bit.ly/ReFigure_ACIR
The detailed molecular characterization of lethal cancers is a prerequisite to understanding resistance to therapy and escape from cancer immunoediting. We performed extensive multi-platform profiling of multi-regional metastases in autopsies from 10 patients with therapy-resistant breast cancer. The integrated genomic and immune landscapes show that metastases propagate and evolve as communities of clones, reveal their predicted neo-antigen landscapes, and show that they can accumulate HLA loss of heterozygosity (LOH). The data further identify variable tumor microenvironments and reveal, through analyses of T cell receptor repertoires, that adaptive immune responses appear to co-evolve with the metastatic genomes. These findings reveal in fine detail the landscapes of lethal metastatic breast cancer.
Author Info: (1) Department of Oncology and Cancer Research UK Cambridge Institute, Li Ka Shing Centre, University of Cambridge, Cambridge CB2 0RE, UK; Vall d'Hebron Institute of Oncology (VHIO
Author Info: (1) Department of Oncology and Cancer Research UK Cambridge Institute, Li Ka Shing Centre, University of Cambridge, Cambridge CB2 0RE, UK; Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron University Hospital, Barcelona 08035, Spain. (2) Department of Oncology and Cancer Research UK Cambridge Institute, Li Ka Shing Centre, University of Cambridge, Cambridge CB2 0RE, UK. (3) Department of Oncology and Cancer Research UK Cambridge Institute, Li Ka Shing Centre, University of Cambridge, Cambridge CB2 0RE, UK. (4) Department of Medicine, University of Cambridge, Cambridge CB2 0QQ, UK. (5) Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel. (6) Center for Noninvasive Diagnostics, Translational Genomics Research Institute, Phoenix, AZ 85004, USA; Mayo Clinic Center for Individualized Medicine, Scottsdale, AZ, USA. (7) Department of Medical Genetics, The Clinical School, University of Cambridge, Cambridge CB2 0QQ, UK. (8) Cancer Molecular Diagnosis Laboratory, NIHR Cambridge Biomedical Research Centre, Cambridge, UK. (9) The Broad Institute, Cambridge, MA 02142, USA; Massachusetts General Hospital Cancer Center and Department of Pathology, Charlestown, MA 02129, USA. (10) Department of Oncology and Cancer Research UK Cambridge Institute, Li Ka Shing Centre, University of Cambridge, Cambridge CB2 0RE, UK. (11) Department of Oncology and Cancer Research UK Cambridge Institute, Li Ka Shing Centre, University of Cambridge, Cambridge CB2 0RE, UK. (12) Department of Oncology and Cancer Research UK Cambridge Institute, Li Ka Shing Centre, University of Cambridge, Cambridge CB2 0RE, UK. (13) Center for Noninvasive Diagnostics, Translational Genomics Research Institute, Phoenix, AZ 85004, USA; Mayo Clinic Center for Individualized Medicine, Scottsdale, AZ, USA. (14) Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron University Hospital, Barcelona 08035, Spain; Spanish Biomedical Research Network Centre in Oncology (CIBERONC), Madrid, Spain. (15) Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron University Hospital, Barcelona 08035, Spain; Spanish Biomedical Research Network Centre in Oncology (CIBERONC), Madrid, Spain. (16) Department of Oncology and Cancer Research UK Cambridge Institute, Li Ka Shing Centre, University of Cambridge, Cambridge CB2 0RE, UK. (17) Department of Oncology and Cancer Research UK Cambridge Institute, Li Ka Shing Centre, University of Cambridge, Cambridge CB2 0RE, UK. (18) Department of Oncology and Cancer Research UK Cambridge Institute, Li Ka Shing Centre, University of Cambridge, Cambridge CB2 0RE, UK. (19) Institute of Astronomy, University of Cambridge, Cambridge CB3 0HA, UK. (20) Department of Medical Genetics, The Clinical School, University of Cambridge, Cambridge CB2 0QQ, UK. (21) Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel. (22) Department of Pathology, Vall d'Hebron University Hospital, 08035 Barcelona, Spain. (23) Spanish Biomedical Research Network Centre in Oncology (CIBERONC), Madrid, Spain; Department of Pathology, Vall d'Hebron University Hospital, 08035 Barcelona, Spain. (24) Spanish Biomedical Research Network Centre in Oncology (CIBERONC), Madrid, Spain; Department of Pathology, Vall d'Hebron University Hospital, 08035 Barcelona, Spain; Translational Molecular Pathology, Vall d'Hebron Research Institute (VHIR), Universitat Autonoma de Barcelona, 08035 Barcelona, Spain. (25) Spanish Biomedical Research Network Centre in Oncology (CIBERONC), Madrid, Spain; Department of Pathology, Vall d'Hebron University Hospital, 08035 Barcelona, Spain; Translational Molecular Pathology, Vall d'Hebron Research Institute (VHIR), Universitat Autonoma de Barcelona, 08035 Barcelona, Spain. (26) Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron University Hospital, Barcelona 08035, Spain; Ramon y Cajal Hospital, 28034 Madrid, Spain. (27) Cancer Molecular Diagnosis Laboratory, NIHR Cambridge Biomedical Research Centre, Cambridge, UK; Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK; Wellcome Trust/MRC Cambridge Stem Cell Institute, Cambridge, UK. (28) The Broad Institute, Cambridge, MA 02142, USA; Massachusetts General Hospital Cancer Center and Department of Pathology, Charlestown, MA 02129, USA. (29) Department of Medical Genetics, The Clinical School, University of Cambridge, Cambridge CB2 0QQ, UK. (30) Center for Noninvasive Diagnostics, Translational Genomics Research Institute, Phoenix, AZ 85004, USA; Mayo Clinic Center for Individualized Medicine, Scottsdale, AZ, USA. (31) Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel. (32) Department of Oncology and Cancer Research UK Cambridge Institute, Li Ka Shing Centre, University of Cambridge, Cambridge CB2 0RE, UK. (33) Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron University Hospital, Barcelona 08035, Spain; Spanish Biomedical Research Network Centre in Oncology (CIBERONC), Madrid, Spain; Institucio Catalana de Recerca i Estudis Avancats (ICREA), Barcelona 08010, Spain. Electronic address: jseoane@vhio.net. (34) Department of Oncology and Cancer Research UK Cambridge Institute, Li Ka Shing Centre, University of Cambridge, Cambridge CB2 0RE, UK; Breast Cancer Programme, Cancer Research UK Cambridge Cancer Centre, Cambridge CB2 2QQ, UK. Electronic address: carlos.caldas@cruk.cam.ac.uk.
