Patterns of immune infiltration and survival in endocrine therapy-treated ER-positive breast cancer: A computational study of 1900 patients

Tumor-infiltrating immune cells (TIICs) play a critical role in breast cancer (BC) prognosis, but little is known regarding the efficacy of endocrine therapy in patients with ER-positive BC with diverse immunological phe-notypes. To investigate whether TIICs affect survival after endocrine therapy in patients with different BC mo-lecular subtypes, data were gathered from six studies totaling 1900 samples. CIBERSORTx was used to analyze the invasion of 22 immune cell subpopulations using a bulk gene expression profile. The relationships of immune-related metagenes and immune cell subsets with survival (distant metastasis-free survival, relapse-free survival, and overall survival) were studied using Cox regression models with cell proportions modeled in quartiles. The immune score and IGHG3 and LCK gene activity were linked to a better prognosis. Among the immune cells, monocytes, resting CD4+ memory T cells and plasma cells were correlated with prolonged sur-vival, while neutrophils, Tregs, M0 macrophages, and M2 macrophages were associated with an unfavorable prognosis. Similar effects were reported for the luminal A subtype. In the luminal B subtype, gamma 8 T cells and eosinophils were favorable prognostic factors. Covariate-adjusted multivariate Cox regression analysis revealed that high proportions of resting CD4+ memory T cells and resting dendritic cells were correlated with a good prognosis. Meanwhile, neutrophils were associated with an unfavorable prognosis. Understanding how mono-cytes and macrophages interact in the tumor microenvironment may be a promising study focus. Comprehensive research on the cellular immune response in tumors could help facilitate the development of new treatments.