Pathologic complete response to neoadjuvant chemotherapy of breast carcinoma is associated with the disappearance of tumor-infiltrating Foxp3+ regulatory T cells
Pathologic complete response to neoadjuvant chemotherapy of breast carcinoma is associated with the disappearance of tumor-infiltrating Foxp3+ regulatory T cells
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DOI：
10.1158/1078-0432.ccr-07-4491
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发表时间：
2008-04-15
影响因子：
11.5
通讯作者：
Ghiringhelli, Francois
中科院分区：
文献类型：
--
作者：
Ladoire, Sylvain;Arnould, Laurent;Ghiringhelli, Francois
目的：在许多癌症中，T细胞浸润与良好的肿瘤预后相关。为了评估新辅助化疗对乳腺癌中T细胞浸润的影响能力，我们评估了CD3和CD8浸润以及Foxp3免疫抑制性T细胞。实验设计：通过免疫组化检测了56例乳腺癌患者在新辅助化疗结束前后的CD3（+）、CD8（+）和Foxp3（+）细胞浸润。不良预后因素（阴性激素受体、高肿瘤分级和淋巴结受累）与化疗开始前CD3、CD8和Foxp3浸润数量显著增加相关。化疗导致Foxp3浸润减少，而CD8和CD3浸润水平保持不变。病理学完全应答（pCR）组Foxp3（+）细胞急剧减少，而无应答者组Foxp3（+）细胞仍然升高。结合手术标本上高CD8浸润和无Foxp3细胞浸润的临界标准与pCR相关，敏感性为75%，特异性为93%。仅在pCR患者中，化疗后细胞毒性TiA1和颗粒酶B阳性细胞的浸润显著增强。通过多变量分析，最终组织学标本的高CD8浸润和无Foxp3浸润的关联独立与pCR.Conclusion：这些研究结果表明，pCR新辅助化疗与免疫学特征相结合的情况下，免疫抑制Foxp3细胞和大量的CD8 T细胞和细胞毒性细胞的存在下。这些结果表明，化疗诱导的抗肿瘤免疫反应。
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.