Converging and evolving immuno-genomic routes toward immune escape in breast cancer
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 breas...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-02-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-45292-1 |
| _version_ | 1797273931764203520 |
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| author | Juan Blanco-Heredia Carla Anjos Souza Juan L. Trincado Maria Gonzalez-Cao Samuel Gonçalves-Ribeiro Sara Ruiz Gil Dmytro Pravdyvets Samandhy Cedeño Maurizio Callari Antonio Marra Andrea M. Gazzo Britta Weigelt Fresia Pareja Theodore Vougiouklakis Achim A. Jungbluth Rafael Rosell Christian Brander Francesc Tresserra Jorge S. Reis-Filho Daniel Guimarães Tiezzi Nuria de la Iglesia Holger Heyn Leticia De Mattos-Arruda |
| author_facet | Juan Blanco-Heredia Carla Anjos Souza Juan L. Trincado Maria Gonzalez-Cao Samuel Gonçalves-Ribeiro Sara Ruiz Gil Dmytro Pravdyvets Samandhy Cedeño Maurizio Callari Antonio Marra Andrea M. Gazzo Britta Weigelt Fresia Pareja Theodore Vougiouklakis Achim A. Jungbluth Rafael Rosell Christian Brander Francesc Tresserra Jorge S. Reis-Filho Daniel Guimarães Tiezzi Nuria de la Iglesia Holger Heyn Leticia De Mattos-Arruda |
| author_sort | Juan Blanco-Heredia |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-07T14:51:11Z |
| format | Article |
| id | doaj.art-14cae652f3b14f88b2b7c2b80f375b63 |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-07T14:51:11Z |
| publishDate | 2024-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-14cae652f3b14f88b2b7c2b80f375b632024-03-05T19:39:54ZengNature PortfolioNature Communications2041-17232024-02-0115111810.1038/s41467-024-45292-1Converging and evolving immuno-genomic routes toward immune escape in breast cancerJuan Blanco-Heredia0Carla Anjos Souza1Juan L. Trincado2Maria Gonzalez-Cao3Samuel Gonçalves-Ribeiro4Sara Ruiz Gil5Dmytro Pravdyvets6Samandhy Cedeño7Maurizio Callari8Antonio Marra9Andrea M. Gazzo10Britta Weigelt11Fresia Pareja12Theodore Vougiouklakis13Achim A. Jungbluth14Rafael Rosell15Christian Brander16Francesc Tresserra17Jorge S. Reis-Filho18Daniel Guimarães Tiezzi19Nuria de la Iglesia20Holger Heyn21Leticia De Mattos-Arruda22IrsiCaixa, Germans Trias i Pujol University HospitalIrsiCaixa, Germans Trias i Pujol University HospitalCentro Nacional de Análisis Genómico (CNAG)Dexeus Institute of Oncology, Quironsalud GroupVall d’Hebron Institute of Oncology (VHIO), Vall d’Hebron University HospitalCentro Nacional de Análisis Genómico (CNAG)OmniscopeIrsiCaixa, Germans Trias i Pujol University HospitalCancer Research UK Cambridge Institute, Robinson WayDepartment of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer CenterDepartment of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer CenterDepartment of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer CenterDepartment of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer CenterDepartment of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer CenterDepartment of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer CenterDexeus Institute of Oncology, Quironsalud GroupIrsiCaixa, Germans Trias i Pujol University HospitalDexeus Institute of Oncology, Quironsalud GroupDepartment of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer CenterDepartment of Gynecology and Obstetrics - Breast Disease Division and Laboratory for Translational Data Science, Ribeirao Preto Medical School, University of Sao PauloIrsiCaixa, Germans Trias i Pujol University HospitalCentro Nacional de Análisis Genómico (CNAG)IrsiCaixa, Germans Trias i Pujol University HospitalAbstract 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.https://doi.org/10.1038/s41467-024-45292-1 |
| spellingShingle | Juan Blanco-Heredia Carla Anjos Souza Juan L. Trincado Maria Gonzalez-Cao Samuel Gonçalves-Ribeiro Sara Ruiz Gil Dmytro Pravdyvets Samandhy Cedeño Maurizio Callari Antonio Marra Andrea M. Gazzo Britta Weigelt Fresia Pareja Theodore Vougiouklakis Achim A. Jungbluth Rafael Rosell Christian Brander Francesc Tresserra Jorge S. Reis-Filho Daniel Guimarães Tiezzi Nuria de la Iglesia Holger Heyn Leticia De Mattos-Arruda Converging and evolving immuno-genomic routes toward immune escape in breast cancer Nature Communications |
| title | Converging and evolving immuno-genomic routes toward immune escape in breast cancer |
| title_full | Converging and evolving immuno-genomic routes toward immune escape in breast cancer |
| title_fullStr | Converging and evolving immuno-genomic routes toward immune escape in breast cancer |
| title_full_unstemmed | Converging and evolving immuno-genomic routes toward immune escape in breast cancer |
| title_short | Converging and evolving immuno-genomic routes toward immune escape in breast cancer |
| title_sort | converging and evolving immuno genomic routes toward immune escape in breast cancer |
| url | https://doi.org/10.1038/s41467-024-45292-1 |
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