Revealing the Interactions of Regulatory Factors in the Immune Microenvironment of Breast Cancer Based on Two-Way Orthogonal Partial Least Square Model and Cell Communication.

The treatment with immune checkpoint inhibitors is not universally effective, and the efficacy is challenging to predict using a single biomarker. Breast cancer (BC) cells develop within a complex microenvironment, which includes tumor cells, immune cells, and extracellular matrix, and they may interact through paracrine signaling. Elucidating the mechanisms of immune microenvironment regulation and intercellular interactions in BC is fundamental for screening efficacy markers and developing new immunotherapeutic targets. Based on the immune phenotype cellular infiltration characteristics and transcriptomic changes, we constructed a two-way orthogonal partial least square (O2PLS) model to identify immune cell infiltration (ICI) genes, quantitatively characterizing the immune microenvironment within BC to predict patient prognosis, select sensitive populations for immunotherapy, and provide a theoretical basis for the combination of immunotherapy with radiotherapy and chemotherapy. We described the T cell differentiation trajectories and intercellular communication landscapes and revealed the synergistic effects of receptors and ligands (CXCL9-CXCR3, CCL5-ACKR1, and GZMA-F2R) on the immune microenvironment and prognosis. These findings may contribute to elucidating the factors that shape the immune microenvironment and identifying new therapeutic targets.