Portal de investigación
High numbers of circulating CD57+ NK cells associate with resistance to HER2-specific therapeutic antibodies in HER2+ primary breast cancer.
Fecha de publicación:
Fecha Ahead of Print:
Autores de INCLIVA
Participantes ajenos a INCLIVA
- Muntasell, Aura
- Servitja, Sonia
- Cabo, Mariona
- Perez-Buira, Sandra
- Rojo, Federico
- Costa-Garcia, Marcel
- Arpi, Oriol
- Moraru, Manuela
- Serrano, Laia
- Tusquets, Ignasi
- Heredia, Gemma
- Vera, Andrea
- Martinez-Garcia, Maria
- Soria, Laura
- Comerma, Laura
- Santana-Hernandez, Sara
- Rovira, Ana
- Vilches, Carlos
- Albanell, Joan
- Lopez-Botet, Miguel
Grupos y Plataformas de I+D+i
Abstract
Natural killer (NK) cells can orchestrate effective antitumor immunity. The presence of tumor-infiltrating NK cells in diagnostic biopsies predicts pathologic complete response (pCR) to HER2-specific therapeutic antibodies in patients with primary breast cancer. Here, we analyzed whether diversity in circulating NK cells might influence tumor infiltration and HER2-specific therapeutic antibody efficacy. We found that numbers of circulating CD57(+) NK cells inversely correlated with pCR to HER2-specific antibody treatment in patients with primary breast cancer independently of age, traditional clinicopathologic factors, and CD16A 158F/V genotype. This association was uncoupled from the expression of other NK-cell receptors, the presence of adaptive NK cells, or changes in major T-cell subsets, reminiscent of cytomegalovirus-induced immunomodula-tion. NK-cell activation against trastuzumab-coated HER2 thorn breast cancer cells was comparable in patients with high and low proportions of CD57(+) NK cells. However, circulating CD57(+) NK cells displayed decreased CXCR3 expression and CD16A-induced IL2-dependent proliferation in vitro. Presence of CD57(+) NK cells was reduced in breast tumorassociated infiltrates as compared with paired peripheral blood samples, suggesting deficient homing, proliferation, and/or survival of NK cells in the tumor niche. Indeed, numbers of circulating CD57(+) were inversely related to tumor-infiltrating NK-cell numbers. Our data reveal that NK-cell differentiation influences their antitumor potential and that CD57(+) NK cells may be a biomarker useful for tailoring HER2 antibody-based therapeutic strategies in breast cancer.
2019 American Association for Cancer Research.
Datos de la publicación
- ISSN/ISSNe:
- 2326-6066, 2326-6074
- Tipo:
- Article
- Páginas:
- 1280-1292
- PubMed:
- 31189644
Cancer Immunology Research American Association for Cancer Research Inc.
Citas Recibidas en Web of Science: 29
Documentos
Filiaciones
Financiación
Proyectos y Estudios Clínicos
Papel de la heterogeneidad tumoral y la reprogramación dinámica de la célula tumoral en la resistencia a anticuerpos anti-HER2 en cáncer de mama HER2 positivo
Investigador Principal: ANA LLUCH HERNÁNDEZ
PI15/01617 . INSTITUTO SALUD CARLOS III . 2016
Plataformas biobancos PT17/0015/0049
Investigador Principal: ANTONIO FERRANDEZ IZQUIERDO
PT17/0015/0049 . INSTITUTO SALUD CARLOS III . 2018
Caracterizacion y repercusion terapeutica de la ecologia de cancer de mama HER2 positivo
Investigador Principal: PILAR EROLES ASENSIO
PI18/01219 . INSTITUTO SALUD CARLOS III . 2019
Cita
Muntasell A,Servitja S,Cabo M,Bermejo B,Perez S,Rojo F,Costa M,Arpi O,Moraru M,Serrano L,Tusquets I,Martinez MT,Heredia G,Vera A,Martinez M,Soria L,Comerma L,Santana S,Eroles P,Rovira A,Vilches C,Lluch A,Albanell J,Lopez M. High numbers of circulating CD57+ NK cells associate with resistance to HER2-specific therapeutic antibodies in HER2+ primary breast cancer. Cancer Immunol Res. 2019. 7. (8):p. 1280-1292. IF:8,728. (1).
High numbers of circulating CD57+ NK cells associate with resistance to HER2-specific therapeutic antibodies in HER2+ primary breast cancer. Muntasell A, Servitja S, Cabo M, Bermejo B, Perez S, Rojo F, Costa M et al. Cancer Immunology Research. 2019 enero 01. 7 (8):1280-1292. DOI:10.1158/2326-6066.CIR-18-0896. PMID:31189644.
