Immune organization defines adaptive immune competence and clinical outcome in breast cancer

作者：Esther Sanfeliu, Elia Seguí, Anabel Martínez-Romero, Víctor Albarrán, Tomás Pascual, Mercedes Marin, Olga Martínez‐Sáez, R Gómez-Bravo, Isabel García-Fructuoso, Adela Rodriguez-Hernandez, Benjamin Walbaum, Patricia Galván, Laura Angelats, Carlota Rubio-Pérez, Cristina Saura, M Oliveira, Eva Ciruelos, Luís Manso, Sònia Pernas, María Vidal, A Waks, Sara M Tolaney, Laia Pare, Joel S. Parker, Patricia Villagrasa, Juan Manuel Ferrero-Cafiero, Charles M. Perou, Elı́as Campo, Josep Tabernero, Fara Braso-Maristany, Aleix Prat · 发表于：medRxiv · 年份：2026 · DOI：10.64898/2026.07.17.26358324 · 研究领域：Cancer Immunotherapy and Biomarkers、Ferroptosis and cancer prognosis、Immunotherapy and Immune Responses

Summary Tumor-infiltrating lymphocytes (TILs) are widely used to assess antitumor immunity in breast cancer but may not reflect the functional competence of adaptive immune responses. We show that immune organization, reflected by tertiary lymphoid structures (TLS) and coordinated humoral and cellular immune programs, represents a distinct dimension of tumor immunity beyond lymphocyte abundance. By integrating histologic, transcriptomic, spatial, and immune receptor profiling analyses across multiple breast cancer cohorts, we show that immune organization is associated with greater immune repertoire diversity, evidence of therapy-induced clonal selection, and improved clinical outcomes, independent of immune infiltration. Transcriptomic measures of immune organization retained independent prognostic value across external cohorts, whereas measures of immune infiltration did not. Furthermore, treatment-induced increases in immune organization, but not immune infiltration, were associated with therapeutic response. These findings identify immune organization as a dynamic and clinically measurable state of adaptive antitumor immunity with implications for prognosis, treatment monitoring, and therapeutic development in breast cancer. One Sentence Summary Spatially organized immune responses, rather than lymphocyte abundance alone, define clinically relevant antitumor immunity in breast cancer.