Tumor-infiltrating Treg, MDSC, and IDO expression associated with outcomes of neoadjuvant chemotherapy of breast cancer
Tumor-infiltrating Treg, MDSC, and IDO expression associated with outcomes of neoadjuvant chemotherapy of breast cancer
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肿瘤浸润 Treg、MDSC 和 IDO 表达与乳腺癌新辅助化疗的结果相关。
DOI：
10.1080/15384047.2018.1450116
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发表时间：
2018-01-01
影响因子：
3.6
通讯作者：
Liu, Juntian
中科院分区：
文献类型：
--
作者：
Li, Fangxuan;Zhao, Yang;Liu, Juntian
背景资料：调节性T细胞（TCFs）和髓源性抑制细胞（MDSC）代表了两种免疫抑制细胞群，它们在建立和维持癌症免疫耐受中非常重要。方法：采用免疫组织化学方法，对乳腺癌组织行新辅助化疗（Neoadjuvant chemotherapy，NCT）前穿刺活检，检测CD 33、Foxp 3和IDO的表达，分析其与乳腺癌治疗反应的相关性。免疫组化双标显示IDO在CD 33（+）MDSCs中的表达与Foxp 3（+）TcB呈正相关（P < 0.05）。CD 33（+）MDSCs、Foxp 3（+）TcB、IDO表达与NCT前临床分期有关（P < 0.05）。CD 33（+）MDSCs、Foxp 3（+）Tf 3、IDO表达、CD 33（+）MDSCs中IDO表达、NCT前临床T3-T4分期、病理T3-T4分期、ER（+）、管腔型与PD+SD的临床疗效相关（P < 0.05）。多因素分析显示，CD 33（+）MDSCs、IDO表达、CD 33（+）MDSCs中IDO表达、病理T分期为PD+SD的危险因素。在NCT的pCR方面，只有CD 33（+）MDSC、临床T3-T4和N1-N3期与无pCR相关（P < 0.05）。多因素分析显示，晚期临床T分期和N分期是无pCR的危险因素。NCT前的临床分期与无进展生存期显著相关（P = 0.021），而Foxp 3（+）T淋巴结转移和临床T分期与总生存期显著相关（分别为P = 0.022和P = 0.001）。通过考克斯回归调整协变量后，Foxp 3（+）Treg是总生存期的重要危险因素。结论：肿瘤浸润MDSC、Treg、IDO表达和MDSC中IDO表达与乳腺癌患者的临床病理特征、NCT反应和预后相关，表明它们可能是NCT临床结果的潜在标志物，有助于临床决策以改善乳腺癌治疗。
Background: Regulatory T cells(Tregs) and myeloid-derived suppressor cells(MDSCs) represent two immunosuppressive cell populations that are important in the establishment and maintenance of cancer immune tolerance. MDSCs can express IDO and promote immune tolerance via expansion of Treg cell.Method: We use needle biopsy breast cancer tissues prior to neoadjuvant chemotherapy(NCT) staining for CD33, Foxp3 and IDO by immunohistochemistry to evaluate whether they were correlated with subsequent treatment responses in breast cancer.Results: Expressions of IDO, CD33(+)MDSCs and Foxp3(+)Tregs were correlated with each other. Immunohistochemical double staining revealed that IDO expression in CD33(+)MDSCs was positively correlated with Foxp3(+)Tregs (P < 0.05). CD33(+)MDSCs, Foxp3(+)Tregs, and IDO expression in tumor tissues were associated with advanced clinical stage prior to NCT (P < 0.05). CD33(+)MDSCs, Foxp3(+)Tregs, IDO expression, IDO expression in CD33(+)MDSCs and clinical T3-T4 stage prior to NCT, pathological T3-T4 stage, ER(+), luminal type were correlated with clinical responses of PD+SD (P < 0.05). Multivariate analysis showed that CD33(+)MDSCs, IDO expression, IDO expression in CD33(+)MDSCs, and advanced pathological T stage were risk factors for PD+SD. Focusing on the pCR of NCT, only CD33(+)MDSCs, clinical T3-T4, and N1-N3 stage prior to NCT were associated with no-pCR (P < 0.05). The multivariate analysis showed that advanced clinical T stage and N stage were risk factors for no-pCR. Clinical stage prior to NCT were significantly correlated with progression free survival (P = 0.021), while Foxp3(+)Tregs and clinical T stage were significantly correlated with overall survival (P = 0.022 and P = 0.001, respectively). Foxp3(+)Treg was significant risk factor for overall survival after adjusting covariates by COX regression.Conclusion: Tumor-infiltrating MDSCs, Tregs, IDO expression and IDO expression in MDSCs were correlated with clinicopathological features, NCT response, and prognosis of breast cancer patients, suggesting that they might be potential markers for clinical outcomes of NCT and help clinical decision-making for improved therapies for breast cancer.