Study on the Significance of Intratumoral CD8⁺/FOXP3⁺ Ratio in Predicting Outcomes of Neoadjuvant Therapy in Breast Cancer

Objective The role of this research is to investigate the relationship between the ratio of CD8⁺/FOXP3⁺ tumor-infiltrating level and the neoadjuvant therapy (NAT) response and prognosis in breast cancer, and to observe the dynamic change before and after NAT.

Methods A total of 104 cases of breast cancer between pre- and post-NAT were collected from January 2014 to November 2018 in Affiliated Cancer Hospital & Institute of Guangzhou Medical University; 104 paired pre- and post-neoadjuvant biopsieswere stained using fluorescent multiplex immunohistochemistry (mIHC); Immune cell subsets were quantified using artificial intelligence (AI)-based methods. SPSS 25.0 was used to detect the predictive value of the ratio of tumor-infiltrating CD8⁺/FOXP3⁺ to pathological complete response (pCR), disease free survival (DFS), overall survival (OS), and the dynamic change of the ratio of tumor-infiltrating CD8⁺/FOXP3⁺ between pre- and post-NAT.

Results Receiver operating characteristic(ROC)analysis indicted that CD8⁺/FOXP3⁺ ratio in the Total region, Stromal region and Intratumoral region were statistically significant and independent predictors of pCRarea under the curve(AUC)=0.679, 0.657, 0.664, DFS(AUC=0.633, 0.617, 0.619)and OS (AUC=0.682, 0.704, 0.691), respectively. Meanwhile, survival analysis also showed that patients with a high CD8⁺/FOXP3⁺ ratio had longer DFS(P=0.002)and OS(P=0.002). Dynamic analysis suggested that the Total region, Stromal region CD8⁺/FOXP3⁺ ratio increased after NAT in the non-pCR people.

Conclusions The ratio of tumor-infiltrating CD8⁺/FOXP3⁺ has a good predictive value for the NAT response and prognosis in breast cancer. Meanwhile, NAT could promote the Total, Stromal tumor-infiltrating level of CD8⁺/FOXP3⁺ ratio in breast cancer.