This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Ladoire, S. Articles by Ghiringhelli, F. PubMed PubMed Citation Articles by Ladoire, S. Articles by Ghiringhelli, F.

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

Authors' Affiliations: ¹ Centre Régional de Lutte Contre le Cancer and ² Institut National de la Sante et de la Recherche Medicale CRI-866, Faculty of Medicine, Dijon, France; and ³ Institut Gustave Roussy, Villejuif, France

Requests for reprints: François Ghiringhelli, Centre Georges Francois Leclerc, Centre de Recherche INSERM 866, Faculté de Médecine, 7 boulevard Jeanne D'Arc, 21000 Dijon, France. Phone: 33-3-80-39-33-53; Fax: 33-3-80-39-34-34; E-mail: francois.ghiringhelli{at}wanadoo.fr.

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.