Converging and evolving immuno-genomic routes toward immune escape in breast cancer
Blanco-Heredia, Juan (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Anjos-Souza, Carla (Institut Germans Trias i Pujol)
Trincado Alonso, Juan Luis, 1987- (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
González-Cao, María (Dexeus Institute of Oncology (Barcelona))
Goncąlves-Ribeiro, Samuel (Vall d'Hebron Institut d'Oncologia)
Ruiz Gil, Sara (Centro Nacional de Análisis Genómico (Barcelona))
Pravdyvets, Dmytro (Omniscope (Barcelona))
Cedeño, Samandhy (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Callari, Maurizio (Cancer Research UK Cambridge Institute)
Marra, Antonio (Memorial Sloan Kettering Cancer Center)
Gazzo, Andrea M. (Memorial Sloan Kettering Cancer Center)
Weigelt, Britta (Memorial Sloan Kettering Cancer Center)
Pareja, Fresia (Memorial Sloan Kettering Cancer Center)
Vougiouklakis, Theodore (Memorial Sloan Kettering Cancer Center)
Jungbluth, Achim A. (Memorial Sloan Kettering Cancer Center)
Rosell, Rafael (Dexeus Institute of Oncology (Barcelona))
Brander, Christian (Universitat de Vic)
Tresserra, Francesc (Dexeus Institute of Oncology (Barcelona))
Reis-Filho, Jorge S (Memorial Sloan Kettering Cancer Center)
Tiezzi, Daniel Guimarães (Union of the Colleges of the Great Lakes (Brasil))
de la Iglesia, Nuria (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Heyn, Holger (Omniscope (Barcelona))
De Mattos-Arruda, Leticia (Institut Germans Trias i Pujol)

Date:	2024
Abstract:	The interactions between tumor and immune cells along the course of breast cancer progression remain largely unknown. Here, we extensively characterize multiple sequential and parallel multiregion tumor and blood specimens of an index patient and a cohort of metastatic triple-negative breast cancers. We demonstrate that a continuous increase in tumor genomic heterogeneity and distinct molecular clocks correlated with resistance to treatment, eventually allowing tumors to escape from immune control. TCR repertoire loses diversity over time, leading to convergent evolution as breast cancer progresses. Although mixed populations of effector memory and cytotoxic single T cells coexist in the peripheral blood, defects in the antigen presentation machinery coupled with subdued T cell recruitment into metastases are observed, indicating a potent immune avoidance microenvironment not compatible with an effective antitumor response in lethal metastatic disease. Our results demonstrate that the immune responses against cancer are not static, but rather follow dynamic processes that match cancer genomic progression, illustrating the complex nature of tumor and immune cell interactions.
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Breast Neoplasms ; Female ; Genomics ; Humans ; Triple Negative Breast Neoplasms ; Tumor Microenvironment
Published in:	Nature communications, Vol. 15 Núm. 1 (december 2024) , p. 1302, ISSN 2041-1723

DOI: 10.1038/s41467-024-45292-1
PMID: 38383522

18 p, 3.3 MB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP) > Josep Carreras Leukaemia Research Institute
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Articles > Published articles