Neoadjuvant treatment of esophageal cancer: Immunosuppression following combined radiochemotherapy

Neoadjuvant treatment of esophageal cancer: Immunosuppression following combined radiochemotherapy
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DOI:
10.1067/msy.2002.127166
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发表时间:
2002-09-01
期刊:
影响因子:
3.8
通讯作者:
Holzmann, B
Holzmann, B
中科院分区:
医学2区
文献类型:
--
作者:
Heidecke, CD;Weighardt, H;Holzmann, B

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背景资料。新辅助肿瘤治疗对癌症患者免疫系统的生物学影响在很大程度上是未知的。如果免疫偏离与术后免疫抑制同时发生,可能会特别有害。观察联合放化疗(RCTx)对食管鳞癌患者T细胞功能的影响。外周血单核细胞与细菌超抗原孵育或将浓缩的T细胞暴露于B淋巴瘤细胞提出的超抗原可刺激T细胞的增殖。以CD3和CD28为交联剂诱导T细胞产生细胞因子,用酶联免疫吸附试验检测IL-2、IL-4、IL-10和干扰素-γ的分泌。采用流式细胞术检测T细胞表面人类白细胞抗原-DR(HLADR)分子的表达。接受RCTx治疗的患者的T淋巴细胞在3种独立超抗原刺激下的增殖反应显著降低。经RCTx治疗后,患者外周血单核细胞的抗原提呈能力和T细胞的细胞因子产生能力并未降低。经RCTx治疗后,T细胞表面人类白细胞抗原-DR表达增加。食管鳞癌患者的RCTx导致T淋巴细胞功能抑制。RCTx后T细胞的增殖性缺陷可能与癌症的免疫监视受损以及与食道切除术相关的更高的手术并发症风险有关。
Background. The biologic effects of neoadjuvant tumor therapies on the immune system of cancer patients are largely unknown. Immune deviations may be particularly detrimental if they occur in conjunction with postoperative immunosuppression. The effects of combined radiochemotherapy (RCTx) on T cell functions in patients with squamous cell carcinoma of the esophagus were investigated.Methods. T cell proliferation was stimulated by incubation of peripheral blood mononuclear cells with bacterial superantigens or by exposure of enriched T cells to superantigens presented by B lymphoma cells. Cytokine production of enriched T cells was induced by cross-linking of CD3 and CD28 and the secretion of interleukin (IL)-2, IL-4, IL-10, and interferon-gamma was measured by enzyme-linked immunosorbent assay. T cell expression of human leukocyte antigen-DR (HLA-DR) molecules was determined by flow cytometry.Results. T lymphocytes from patients having undergone RCTx exhibited a significantly reduced proliferative response following stimulation with 3 independent superantigens. Cytokine production of T cells and the antigen presenting capacity of patients peripheral blood mononuclear cells was not diminished following RCTx. T cell expression of HLA-DR was increased following RCTx.Conclusions. RCTx of patients with squamous cell carcinoma of the esophagus results in the suppression of T lymphocyte functions. The proliferative defects of T cells after RCTx may be linked to an impaired immune surveillance of cancer and to a higher risk of surgical complications associated with esophagectomy.