The exact function of M1 macrophages and CXCL9 in forecasting the effectiveness of immune checkpoint inhibitors (ICIs) is still not thoroughly investigated. We investigated the potential of M1 macrophage and C‐X‐C Motif Chemokine Ligand 9 (CXCL9) as predictive markers for ICI efficacy, employing a comprehensive approach integrating multicohort analysis and single‐cell RNA sequencing. A significant correlation between high M1 macrophage and improved overall survival (OS) and objective response rate (ORR) was found. M1 macrophage expression was most pronounced in the immune‐inflamed phenotype, aligning with increased expression of immune checkpoints. Furthermore, CXCL9 was identified as a key marker gene that positively correlated with M1 macrophage and response to ICIs, while also exhibiting associations with immune‐related pathways and immune cell infiltration. Additionally, through exploring RNA epigenetic modifications, we identified Apolipoprotein B MRNA Editing Enzyme Catalytic Subunit 3G (APOBEC3G) as linked to ICI response, with high expression correlating with improved OS and immune‐related pathways. Moreover, a novel model based on M1 macrophage, CXCL9, and APOBEC3G‐related genes was developed using multi‐level attention graph neural network, which showed promising predictive ability for ORR. This study illuminates the pivotal contributions of M1 macrophages and CXCL9 in shaping an immune‐active microenvironment, correlating with enhanced ICI efficacy. The combination of M1 macrophage, CXCL9, and APOBEC3G provides a novel model for predicting clinical outcomes of ICI therapy, facilitating personalized immunotherapy.

HER2-positive breast cancer, characterized by overexpression of the human epidermal growth factor receptor 2 (HER2), accounts for approximately 15-20% of all breast cancers and is associated with aggressive tumor behavior and poor prognosis. Advances in HER2-targeted therapies, such as monoclonal antibodies (trastuzumab, pertuzumab), tyrosine kinase inhibitors (TKIs), and antibody-drug conjugates (ADCs), have significantly improved treatment outcomes in this subtype. Neoadjuvant therapy, administered before surgery, has become a cornerstone in managing HER2-positive breast cancer by improving pathological complete response (pCR) rates and survival outcomes. This review provides a comprehensive analysis of recent advancements in HER2-targeted neoadjuvant therapies, highlighting the mechanisms of action, clinical efficacy, and synergistic effects when combined with chemotherapy. Key challenges, such as treatment-related toxicities, and the potential for personalized treatment strategies based on biomarkers like tumor-infiltrating lymphocytes (TILs) and HER2-enriched subtypes, are discussed. Future directions emphasize optimizing treatment regimens to enhance efficacy while minimizing adverse effects, with novel agents such as trastuzumab deruxtecan (T-DXd) showing promise for expanding the therapeutic landscape.