Intratumoral regulatory T cells as an independent predictive factor for pathological complete response to neoadjuvant paclitaxel followed by 5-FU/epirubicin/cyclophosphamide in breast cancer patients

Abstract

Anti-tumor immunity is thought to play a significant role in chemotherapeutic response of breast tumors. In the present study, we investigated whether tumor infiltrating FOXP3+ regulatory T cells, CD8+ cytotoxic T cells, and IL17F+ helper T cells were associated with a pathological complete response (pCR) to neoadjuvant chemotherapy (NAC). Breast cancer patients (stages II and III, n = 180) who were treated with NAC consisting of sequential weekly paclitaxel followed by 5-FU/epirubicin/cyclophosphamide were included for this study. Core needle tumor specimens obtained before NAC were immunohistochemically examined for FOXP3, CD8, and IL17F. Intratumoral infiltration of FOXP3+, CD8+, and IL17F+ T cells was observed in 62.2, 80.0, and 62.2 % of tumors, respectively. FOXP3 and CD8 infiltrates, but not IL17F infiltrate, were significantly (P < 0.001 and P = 0.007, respectively) associated with a high-pCR rate (31.3 and 25.7 %, respectively), and breast tumors with both FOXP3 and CD8 infiltrates showed the highest pCR rate (33.0 %). Multivariate analysis indicated that only FOXP3 infiltrates (P = 0.014) and the conventional predictive factor Ki67 (P = 0.031) were statistically significant and independent predictors of pCR. Breast tumors with FOXP3 and CD8 infiltrates were more likely to achieve pCR. FOXP3 infiltrate, in combination with Ki67, could thus be used as a clinically useful predictor of response to NAC. The possible indirect mechanism through which chemotherapy exerts its anti-tumor activity, i.e., enhancing anti-tumor immunity by inhibiting FOXP3, was also suggested.

Tumor infiltrating CD8+T lymphocyte count is independent of tumor TLR9 status in treatment naïve triple negative breast cancer and renal cell carcinoma

“…30,33,34,[40][41][42] Furthermore, the specificities of the immune cell infiltrate matter. 43,44 Tumor characteristics that define breast cancer immunophenotype and the way they recruit immune cells are not currently very well understood.…”

Immunology and Immunotherapy of Breast Cancer

“…Likewise, Ladoire et al [ 20 ] reported that a high CD8/FOXP3 ratio was an independent predictive factor of RFS and OS in HER2-overexpressing breast cancer following neoadjuvant chemotherapy. In contrast, Oda et al [ 21 ] reported that a high level of FOXP3 + cells before neoadjuvant chemotherapy was an independent predictor of pathological complete responses. Others have also reported a positive correlation between high levels of FOXP3 + T cells and good prognosis [ 22 , 23 ].…”

Potential of extravasated platelet aggregation as a surrogate marker for overall survival in patients with advanced gastric cancer treated with preoperative docetaxel, cisplatin and S-1: a retrospective observational study

“…The average number of FOXP3-positive T cells was evaluated; ≥5.5 being defined as positive and <5.5 as negative [25]. …”