Pathologic Complete Response to Neoadjuvant Chemotherapy of Breast Carcinoma Is Associated with the Disappearance of Tumor-Infiltrating Foxp3+ Regulatory T …

S Ladoire, L Arnould, L Apetoh, B Coudert, F Martin… - Clinical cancer …, 2008 - AACR
S Ladoire, L Arnould, L Apetoh, B Coudert, F Martin, B Chauffert, P Fumoleau, F Ghiringhelli
Clinical cancer research, 2008AACR
Purpose: T-cell infiltration is associated with good tumor prognosis in many cancers. To
assess the capacity of neoadjuvant chemotherapy to affect T-cell infiltration in breast cancer,
we evaluated CD3 and CD8 infiltrates, and the Foxp3 immunosuppressive T cells.
Experimental Design: CD3+, CD8+, and Foxp3+ cell infiltrates were detected by
immunohistochemistry in a series of 56 breast cancer patients before and after the end of
neoadjuvant chemotherapy. Results: Poor prognostic factors (negative hormonal receptors …
Abstract
Purpose: T-cell infiltration is associated with good tumor prognosis in many cancers. To assess the capacity of neoadjuvant chemotherapy to affect T-cell infiltration in breast cancer, we evaluated CD3 and CD8 infiltrates, and the Foxp3 immunosuppressive T cells.
Experimental Design: CD3+, CD8+, and Foxp3+ cell infiltrates were detected by immunohistochemistry in a series of 56 breast cancer patients before and after the end of neoadjuvant chemotherapy.
Results: Poor prognostic factors (negative hormonal receptors, high tumor grade, and nodal involvement) were associated with a significantly higher number of CD3, CD8, and Foxp3 infiltrates before the beginning of chemotherapy. Chemotherapy resulted in a decrease in Foxp3 infiltrates, whereas the level of CD8 and CD3 infiltrates remained unchanged. Pathologic complete responses (pCR) had a drastic decrease of Foxp3+ cells, whereas these cells remained elevated in nonresponders. A cutoff criterion that combined high CD8 infiltration and no Foxp3 cell infiltration on surgical specimens is associated with pCR with a sensitivity of 75% and a specificity of 93%. The infiltrate of cytotoxic TiA1 and granzyme B–positive cells was dramatically enhanced after chemotherapy only in patients with pCR. By multivariate analysis, association of a high CD8 infiltration and no Foxp3 infiltration on final histologic specimens were independently associated with pCR.
Conclusion: These findings indicate that pCR to neoadjuvant chemotherapy is associated with an immunologic profile combining the absence of immunosuppressive Foxp3 cells and the presence of a high number of CD8 T cells and cytotoxic cells. These results argue for the induction of an antitumor immune response by chemotherapy.
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