Converging and evolving immuno-genomic routes toward immune escape in breast cancer
Por:
Blanco-Heredia, J, Souza, CA, Trincado, JL, Gonzalez-Cao, M, Gonçalves-Ribeiro, S, Gil, SR, Pravdyvets, D, Cedeño, S, Callari, M, Marra, A, Gazzo, AM, Weigelt, B, Pareja, F, Vougiouklakis, T, Jungbluth, AA, Rosell, R, Brander, C, Tresserra, F, Reis, JS, Tiezzi, DG, de la Iglesia, N, Heyn, H and De Mattos-Arruda, L
Publicada:
21 feb 2024
Resumen:
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.
Immune response during breast cancer progression remains to be explored. Here, the characterisation of sequential and parallel multiregion samples of an index patient and a cohort of metastatic triple-negative breast cancers reveals convergent immune evasion mechanisms and an increase in tumor genomic heterogeneity.
Filiaciones:
Blanco-Heredia, J:
Germans Trias i Pujol Univ Hosp, IrsiCaixa, Badalona, Spain
Germans Trias i Pujol Res Inst IGTP, Badalona, Spain
Mem Sloan Kettering Canc Ctr, Dept Pathol & Lab Med, New York, NY USA
Souza, CA:
Germans Trias i Pujol Univ Hosp, IrsiCaixa, Badalona, Spain
Germans Trias i Pujol Res Inst IGTP, Badalona, Spain
Trincado, JL:
Ctr Nacl Anal Genom CNAG, Barcelona, Spain
Josep Carreras Leukemia Res Inst, Barcelona, Spain
Gonzalez-Cao, M:
Dexeus Inst Oncol, Quironsalud Grp, Barcelona, Spain
Gonçalves-Ribeiro, S:
Vall dHebron Univ Hosp, Vall dHebron Inst Oncol VHIO, Barcelona, Spain
Gil, SR:
Ctr Nacl Anal Genom CNAG, Barcelona, Spain
Pravdyvets, D:
Omniscope, Barcelona, Spain
:
Germans Trias i Pujol Univ Hosp, IrsiCaixa, Badalona, Spain
Callari, M:
Canc Res UK Cambridge Inst, Robinson Way, Cambridge, England
Marra, A:
Mem Sloan Kettering Canc Ctr, Dept Pathol & Lab Med, New York, NY USA
Gazzo, AM:
Mem Sloan Kettering Canc Ctr, Dept Pathol & Lab Med, New York, NY USA
Weigelt, B:
Mem Sloan Kettering Canc Ctr, Dept Pathol & Lab Med, New York, NY USA
Pareja, F:
Mem Sloan Kettering Canc Ctr, Dept Pathol & Lab Med, New York, NY USA
Vougiouklakis, T:
Mem Sloan Kettering Canc Ctr, Dept Pathol & Lab Med, New York, NY USA
Jungbluth, AA:
Mem Sloan Kettering Canc Ctr, Dept Pathol & Lab Med, New York, NY USA
Rosell, R:
Dexeus Inst Oncol, Quironsalud Grp, Barcelona, Spain
:
Germans Trias i Pujol Univ Hosp, IrsiCaixa, Badalona, Spain
ICREA, Passeig Lluis Companys 23, Barcelona, Spain
Univ Cent Catalunya, Univ Vic, Catalunya, Spain
Tresserra, F:
Dexeus Inst Oncol, Quironsalud Grp, Barcelona, Spain
Reis, JS:
Mem Sloan Kettering Canc Ctr, Dept Pathol & Lab Med, New York, NY USA
Tiezzi, DG:
Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Gynecol & Obstet, Breast Dis Div, Ribeirao Preto, Brazil
Univ Sao Paulo, Ribeirao Preto Med Sch, Lab Translat Data Sci, Ribeirao Preto, Brazil
Union Coll Great Lakes UNILAGO, Adv Res Ctr Med CEPAM, Sao Jose Do Rio Preto, Brazil
:
Germans Trias i Pujol Univ Hosp, IrsiCaixa, Badalona, Spain
Heyn, H:
Ctr Nacl Anal Genom CNAG, Barcelona, Spain
Omniscope, Barcelona, Spain
De Mattos-Arruda, L:
Germans Trias i Pujol Univ Hosp, IrsiCaixa, Badalona, Spain
Germans Trias i Pujol Res Inst IGTP, Badalona, Spain
gold
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