低基质Foxp3 +调节性T细胞密度与直肠癌新辅助放化疗的完全缓解相关。
Low stromal Foxp3+ regulatory T-cell density is associated with complete response to neoadjuvant chemoradiotherapy in rectal cancer.
作者信息
McCoy M J, Hemmings C, Miller T J, Austin S J, Bulsara M K, Zeps N, Nowak A K, Lake R A, Platell C F
机构信息
St John of God Subiaco Hospital, PO Box 14, Subiaco, WA 6904, Australia.
School of Medicine and Pharmacology, University of Western Australia, M503, 35 Stirling Highway, Crawley, WA 6009, Australia.
出版信息
Br J Cancer. 2015 Dec 22;113(12):1677-86. doi: 10.1038/bjc.2015.427. Epub 2015 Dec 8.
BACKGROUND
Foxp3+ regulatory T cells (Tregs) play a vital role in preventing autoimmunity, but also suppress antitumour immune responses. Tumour infiltration by Tregs has strong prognostic significance in colorectal cancer, and accumulating evidence suggests that chemotherapy and radiotherapy efficacy has an immune-mediated component. Whether Tregs play an inhibitory role in chemoradiotherapy (CRT) response in rectal cancer remains unknown.
METHODS
Foxp3+, CD3+, CD4+, CD8+ and IL-17+ cell density in post-CRT surgical samples from 128 patients with rectal cancer was assessed by immunohistochemistry. The relationship between T-cell subset densities and clinical outcome (tumour regression and survival) was evaluated.
RESULTS
Stromal Foxp3+ cell density was strongly associated with tumour regression grade (P=0.0006). A low stromal Foxp3+ cell density was observed in 84% of patients who had a pathologic complete response (pCR) compared with 41% of patients who did not (OR: 7.56, P=0.0005; OR: 5.27, P=0.006 after adjustment for presurgery clinical factors). Low stromal Foxp3+ cell density was also associated with improved recurrence-free survival (HR: 0.46, P=0.03), although not independent of tumour regression grade.
CONCLUSIONS
Regulatory T cells in the tumour microenvironment may inhibit response to neoadjuvant CRT and may represent a therapeutic target in rectal cancer.
背景
Foxp3+调节性T细胞（Tregs）在预防自身免疫中发挥着至关重要的作用，但也会抑制抗肿瘤免疫反应。Tregs在结直肠癌中的肿瘤浸润具有很强的预后意义，越来越多的证据表明化疗和放疗疗效具有免疫介导成分。Tregs在直肠癌的放化疗（CRT）反应中是否发挥抑制作用尚不清楚。
方法
通过免疫组织化学评估128例直肠癌患者CRT术后手术样本中Foxp3+、CD3+、CD4+、CD8+和IL-17+细胞密度。评估T细胞亚群密度与临床结局（肿瘤退缩和生存）之间的关系。
结果
基质Foxp3+细胞密度与肿瘤退缩分级密切相关（P = 0.0006）。84%达到病理完全缓解（pCR）的患者观察到低基质Foxp3+细胞密度，而未达到pCR的患者中这一比例为41%（比值比：7.56，P = 0.0005；调整术前临床因素后比值比：5.27，P = 0.006）。低基质Foxp3+细胞密度也与无复发生存期改善相关（风险比：0.46，P = 0.03），尽管并非独立于肿瘤退缩分级。
结论
肿瘤微环境中的调节性T细胞可能抑制对新辅助CRT的反应，可能是直肠癌的一个治疗靶点。
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