Intratumoral Stenotrophomonas Maltophilia in Breast Cancer: Unraveling the Interplay with Hormone Receptors and Impact on Tumor Immunity.

Abstract

This study aimed to explore the impact of intratumoral microorganisms in conjunction with hormone receptors on the tumor microenvironment and their potential role in predicting patient prognosis. Significant bacterial variations were identified within ER, PR, HER2, and triple-negative breast cancer subtypes. Kaplan-Meier survival analysis was employed to identify bacteria associated with patient survival. Further, a humanized immune system mouse model bearing breast cancer xenografts was used to evaluate the effects of Stenotrophomonas maltophilia (SMA) on tumor growth and CD8+ T cell infiltration. Additional validation experiments included fluorescence in situ hybridization for SMA, CD8+ T cell chemotaxis, and intracellular cytokine detection. Lawsonella clevelandensis-A, Diaphorobacter nitroreducens, and SMA were identified as significant prognostic species. Notably, tumor-infiltrating immune cells, particularly CD8+ T cells, exhibited a positive association with the presence of SMA. Experimental validation with clinically isolated SMA further confirmed its positive correlation with CD8+ T cell activation. In vivo findings demonstrated that SMA inhibited tumor growth and promoted CD8+ T cell infiltration, highlighting the complex interactions between intratumoral microbiota and tumor immunity in breast cancer. These insights contribute to the understanding of microbial influences on the tumor microenvironment and suggest potential pathways for improving patient prognosis through microbiota modulation.