Breastfeeding shapes a unique tumor-immune landscape in pregnancy-associated breast cancer from GEICAM-EMBARCAM study.
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Peña-Enríquez Regina, Guerrero-Zotano Ángel, Bermejo Begoña, Díaz-Chacon Alejandra, Gilarranz Yolanda Jerez, Lorenzo José JPonce, Cejalvo Juan Miguel, Bertran Ana Santaballa, Galve-Calvo Elena, Aramburo Antonio Fernández, de Ibargüen Blanca Cantos Sánchez, Anton-Torres Antonio, Moreno Fernando, Lopez-Ceballos María Helena, Fernández Yolanda, De La Cruz Susana, Pérez María Eva, Blancas Isabel, Vidal-Losada María, Ruiz-Borrego Manuel, Jiménez-Arranz Álvaro, Ponferrada David, Bautista-Moreno Rocío, Martínez-López Ana, López-Herrero María, Rivas-Crespo Aurora, Rincón Raul, Caballero Rosalía, Martín Miguel, Guil-Luna Silvia, de la Haba-Rodríguez Juan
Аннотация
METHODS: We conducted BC360 NanoString gene expression analysis and CIBERSORTx immune deconvolution in 106 breast cancer cases, including 57 PABC patients stratified by diagnosis stage (gestation, breastfeeding, or post-weaning) and 49 non-PABC controls.
RESULTS: Our study identified a shared aggressive signature across all PABC cases, marked by increased proliferation and impaired DNA repair. Notably, breastfeeding patients (PABC-BF) emerged as a distinct subset, displaying an immune-inflamed tumor profile characterized by elevated inflammatory chemokines, enriched CD8⁺ T-cell and regulatory T-cell infiltration, and prominent TIGIT inhibitory checkpoint upregulation.
CONCLUSIONS: These findings reveal lactation as a physiological framework that shapes tumor immunity, defining a distinct tumor-immune landscape which warrants further investigation for potential therapeutic approaches.