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The Genomic and Immune Landscapes of Lethal Metastatic Breast Cancer

2019; Cell Press; Volume: 27; Issue: 9 Linguagem: Inglês

10.1016/j.celrep.2019.04.098

2639-1856

Leticia De Mattos‐Arruda, Stephen‐John Sammut, Edith Ross, Rachael Bashford-Rogers, Erez Greenstein, Havell Markus, Sandro Morganella, Yvonne H. F. Teng, Yosef E. Maruvka, Bernard Pereira, Oscar M. Rueda, Suet‐Feung Chin, Tania Contente‐Cuomo, Regina Mayor, Alexandra Arias, H. Raza Ali, Wei Cope, Daniel Guimarães Tiezzi, Aliakbar Dariush, Tauanne Dias Amarante, Dan Reshef, Nikaoly Ciriaco, Elena Martínez‐Sáez, Vicente Peg, Santiago Ramón y Cajal, Javier Cortés, George S. Vassiliou, Gad Getz, Serena Nik‐Zainal, Muhammed Murtaza, Nir Friedman, Florian Markowetz, Joan Seoane, Carlos Caldas,

Immunotherapy and Immune Responses

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.