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肿瘤微环境介质 CD8 和 FOXP3 标记的 T 淋巴细胞是接受根治性治疗的直肠癌患者的潜在预后标志物。

Tumor Microenvironment Mediators CD8- and FOXP3-Labeled T Lymphocytes Are Prospective Prognosticators in Curatively Treated Rectal Cancer Patients.

机构信息

Clinical Oncology Department, Faculty of Medicine, Alexandria University, Alexandria, Egypt.

Surgical Oncology Department, National Cancer Institute, Cairo University, Cairo, Egypt.

出版信息

J Gastrointest Cancer. 2021 Mar;52(1):177-186. doi: 10.1007/s12029-020-00376-1.

DOI:10.1007/s12029-020-00376-1
PMID:32112202
Abstract

PURPOSE

To explore the implication of CD8- and FOXP3-labeled T lymphocytes invading tumor microenvironment in prognosticating curatively treated rectal cancer with preoperative chemo-radiation.

METHODS

The diagnostic rectal biopsies from clinical T3-T4 and any nodal diseases or any T stage with nodal involvement were processed to quantify (CD8and FOXP3). The impact of tested indicators on the achieved pathologic response among other clinical-pathological variables was particularized. Additionally, the prognosticating eventuality of labeled T lymphocytes for survival was elaborated using Log-rank and Cox regression.

RESULTS

We selected fifty rectal patients who had negative surgical margins following preoperative chemo-radiation for clinical T3-T4 or any T stage with nodal involvement. The higher expressions of CD8 and CD8/FOXP3, and the reduced FOXP3incursion were interrelated with the lack of nodal and lympho-vascular invasion alongside accentuated pathologic response. Additionally, the augmented densities of FOXP3 ≥ 120, the reduced CD8/FOXP3 ratio < 0.96, and the nodal incursion were considerably linked with the worsened OS [hazard ratio (HR) 2.37 (95% confidence interval (CI), 2.38-11.27), 2.41 (95% CI, 2.14-7.12), and 2.63 (95% CI, 2.81-5.32)], and dismal DFS [HR 2.61 (95% CI, 1.58-6.12), 3.12 (95% CI, 2.15-7.24), and 3.32 (95% CI, 2.47-9.24)], respectively.

CONCLUSION

The augmented expressions of CD8 and C8/FOXP3 together with the reduced densities of FOXP3 exhibited a substantial contribution to the attained pathological response and were linked to improved clinical-pathological characteristics of cancer rectum patients treated with chemo-radiation preceding mesorectal excision. Additionally, they can be authorized as reliable individual prognosticators of clinical outcomes.

摘要

目的

探讨术前放化疗治疗可治愈的直肠癌患者肿瘤微环境中 CD8 和 FOXP3 标记 T 淋巴细胞浸润的意义。

方法

对临床 T3-T4 及任何淋巴结疾病或任何 T 期伴淋巴结受累的直肠活检进行处理,以定量(CD8 和 FOXP3)。特别研究了测试指标对其他临床病理变量之间获得的病理反应的影响。此外,还使用 Log-rank 和 Cox 回归阐述了标记 T 淋巴细胞对生存的预后意义。

结果

我们选择了 50 例接受术前放化疗的临床 T3-T4 或任何 T 期伴淋巴结受累的直肠癌患者,这些患者均有阴性手术切缘。CD8 和 CD8/FOXP3 的高表达以及 FOXP3 浸润的减少与缺乏淋巴结和淋巴管侵犯以及病理反应增强有关。此外,FOXP3≥120 的密度增加、CD8/FOXP3 比值<0.96 以及淋巴结浸润与较差的 OS(风险比 (HR) 2.37(95%置信区间 (CI),2.38-11.27)、2.41(95% CI,2.14-7.12)和 2.63(95% CI,2.81-5.32))和较差的 DFS(HR 2.61(95% CI,1.58-6.12)、3.12(95% CI,2.15-7.24)和 3.32(95% CI,2.47-9.24))密切相关。

结论

CD8 和 C8/FOXP3 的表达增加以及 FOXP3 密度的降低对获得的病理反应有显著贡献,并与接受放化疗后行直肠系膜切除术的直肠癌患者的临床病理特征改善相关。此外,它们可以作为临床结局的可靠个体预后指标。

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T Regulatory Cells and Priming the Suppressive Tumor Microenvironment.调节性 T 细胞与抑制性肿瘤微环境的形成。
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The prognostic value of tumor-infiltrating lymphocytes in colorectal cancer differs by anatomical subsite: a systematic review and meta-analysis.结直肠癌肿瘤浸润淋巴细胞的预后价值因解剖部位不同而不同:系统评价和荟萃分析。
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术前活检中的 I 型干扰素足迹是一个独立的生物标志物,与 CD8 T 细胞定量相结合可以提高对直肠腺癌新辅助治疗反应的预测。
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