Pathologic complete response to neoadjuvant chemotherapy of breast carcinoma is associated with the disappearance of tumor-infiltrating foxp3+ regulatory T cells.
Fiche publication
Date publication
avril 2008
Auteurs
Membres identifiés du Cancéropôle Est :
Dr ARNOULD Laurent, Dr COUDERT Bruno, Pr FUMOLEAU Pierre, Pr GHIRINGHELLI François, Dr LADOIRE Sylvain
Tous les auteurs :
Ladoire S, Arnould L, Apetoh L, Coudert B, Martin F, Chauffert B, Fumoleau P, Ghiringhelli F
Lien Pubmed
Résumé
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.
Référence
Clin Cancer Res. 2008 Apr 15;14(8):2413-20.