三种不同新辅助治疗方案下三阴性乳腺癌的转录组与微环境特征

Adding immunotherapy to chemotherapy can modestly improve the pathological complete response (pCR) rate in triple-negative breast cancer (TNBC), while our previous NeoSAC study demonstrated that combining anti-angiogenic therapy can further enhance pCR. However, research on the mechanisms underlying the efficacy differences and biomarker comparisons across these treatment regimens remains insufficient.

Female TNBC patients were consecutively enrolled into three groups: chemotherapy (chemo), chemo-immunotherapy (chemo-ICI), and chemo-immunotherapy-anti-angiogenesis (chemo-ICI-AA, from our NeoSAC study, NCT04722718). Efficacy and safety were compared, with RNA sequencing and immune microenvironment analyses conducted to explore mechanisms of efficacy differences and identify potential biomarkers.

The total pCR rates in the chemo, chemo-ICI, and chemo-ICI-AA groups were 43.3%, 60.0%, and 72.7%, respectively. Baseline immune profiles were similar across groups, with comparable stromal, immune, and GEP scores. In the chemo-ICI-AA group, higher CD8 + T cells, TH1 cells, and TIL infiltration in pCR patients suggested their potential as biomarkers. Enhanced cytolytic activity, pro-inflammatory pathways, T-cell costimulation, and oxeiptosis correlated with higher pCR rates in the chemo-ICI-AA group. Notably, oxeiptosis has emerged as a potential predictor of treatment response, especially in pCR patients from the chemo-ICI and chemo-ICI-AA groups. Additionally, ALK (p = 0.017) and ATP6V1C2 (p = 0.036) were identified as significant genes in the chemo-ICI-AA pCR group, with predictive value for pCR outcomes.

Adding immunotherapy and anti-angiogenic therapy to chemotherapy progressively increased the pCR rate. We emphasized the critical role of differentially expressed genes and immune microenvironment changes in predicting treatment outcomes.