Converging and evolving immuno-genomic routes toward immune escape in breast cancer Journal Article

   


Authors: Blanco-Heredia, J.; Souza, C. A.; Trincado, J. L.; Gonzalez-Cao, M.; Gonçalves-Ribeiro, S.; Gil, S. R.; Pravdyvets, D.; Cedeño, S.; Callari, M.; Marra, A.; Gazzo, A. M.; Weigelt, B.; Pareja, F.; Vougiouklakis, T.; Jungbluth, A. A.; Rosell, R.; Brander, C.; Tresserra, F.; Reis-Filho, J. S.; Tiezzi, D. G.; de la Iglesia, N.; Heyn, H.; De Mattos-Arruda, L.
Article Title: 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 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. © The Author(s) 2024.
Keywords: genetics; pathology; breast neoplasms; blood; antigen; breast tumor; genomics; tumor; heterogeneity; tumor microenvironment; triple negative breast cancer; procedures; cancer; humans; human; female; convergent evolution; triple negative breast neoplasms
Journal Title: Nature Communications
Volume: 15
ISSN: 2041-1723
Publisher: Nature Publishing Group  
Date Published: 2024-01-01
Start Page: 1302
Language: English
DOI: 10.1038/s41467-024-45292-1
PUBMED: 38383522
PROVIDER: scopus
PMCID: PMC10882008
DOI/URL:

https://www.scopus.com/inward/record.uri?eid=2-s2.0-85185680470&doi=10.1038%2fs41467-024-45292-1&partnerID=40&md5=85b892ee4868b0757d8cdf0c5d0f30aa
Notes: The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PDF -- Source: Scopus
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MSK Authors
  1. Achim Jungbluth
    456 Jungbluth
  2. Britta Weigelt
    633 Weigelt
  3. Jorge Sergio Reis-Filho
    639 Reis-Filho
  4. Fresia Gilda Pareja Zea
    217 Pareja Zea
  5. Andrea Maria Gazzo
    53 Gazzo
  6. Antonio Marra
    45 Marra
  7. Juan Blanco Heredia
    11 Blanco Heredia
  8. Theodore Vougiouklakis
    7 Vougiouklakis
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