HLA class I expression and its alteration by preoperative hyperthermo-chemoradiotherapy in patients with rectal cancer.

HLA class I expression and its alteration by preoperative hyperthermo-chemoradiotherapy in patients with rectal cancer.
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DOI:
10.1371/journal.pone.0108122
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发表时间:
2014
期刊:
影响因子:
3.7
通讯作者:
Nakano T
Nakano T
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Sato H;Suzuki Y;Ide M;Katoh T;Noda SE;Ando K;Oike T;Yoshimoto Y;Okonogi N;Mimura K;Asao T;Kuwano H;Nakano T

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增强免疫应答,包括肿瘤细胞上人类白细胞抗原(human leukocyte antigen,HLA)I类的表达以及肿瘤特异性细胞毒性T淋巴细胞(cytotoxic T lymphocyte,CTL)对肿瘤细胞的识别和清除,被认为是放射治疗的新概念。本研究对局部进展期直肠癌患者行术前高温放化疗(HCRT),以评估HLA I类分子表达与临床结局之间的相关性。入组了78例术前接受HCRT的局部晚期直肠腺癌患者。患者的中位年龄为64岁(范围:33-85岁),分别有4、18和56例患者患有临床I、II和III期疾病。HCRT前后取福尔马林固定石蜡包埋组织,用抗HLA I-A、B、C类抗体进行免疫组化分析。根据肿瘤细胞阳性对HLA I类表达进行分级。在HCRT前,归类为0级和1级的标本数量分别为19(24%)和58(74%)。仅1例患者(1%)显示2级表达。然而,分别有6(8%)、27(35%)、7(9%)和12(15%)例HCRT后标本被分级为0、1、2和3级。HCRT后标本中HLA I类表达显著增加(p<0.01)。然而,无论是前或后HCRT HLA I类表达影响总生存期和无远处转移生存期的临床III期患者。单因素分析显示HCRT后HLA I类分子表达与LC呈显著负相关(p<0.05)。然而,多因素分析显示HLA I类表达与临床结局无相关性。HCRT增加直肠癌患者HLA I类表达。然而,多因素分析未能显示HLA I类表达水平与预后之间的任何相关性。
Enhancing immunologic responses, including human leukocyte antigen (HLA) class I expression on tumor cells and recognition and elimination of tumor cells by tumor-specific cytotoxic T lymphocyte (CTL), is considered a novel concept of radiotherapy. The present study examined patients who underwent preoperative hyperthermo-chemoradiotherapy (HCRT) for locally advanced rectal cancer to assess the correlation between HLA class I expression and clinical outcome. Seventy-eight patients with locally advanced rectal adenocarcinoma who received preoperative HCRT were enrolled. The median age of the patients was 64 years (range, 33–85 years) and 4, 18, and 56 patients had clinical stage I, II and III disease, respectively. Formalin-fixed and paraffin-embedded tissues excised before and after HCRT were subjected to immunohistochemical analysis with an anti-HLA class I-A, B, C antibody. HLA class I expression was graded according to tumor cell positivity. In pre-HCRT, the number of specimens categorized as Grade 0 and 1 were 19 (24%) and 58 (74%), respectively. Only 1 patient (1%) showed Grade 2 expression. However, 6 (8%), 27 (35%), 7 (9%), and 12 (15%) post-HCRT specimens were graded as Grade 0, 1, 2, and 3, respectively. There was a significant increase in HLA class I expression in post-HCRT specimens (p<0.01). However, neither pre- nor post-HCRT HLA class I expression affected overall survival and distant metastasis-free survival in clinical stage III patients. Univariate analysis revealed that Post-HCRT HLA class I expression showed a significant negative relationship with LC (p<0.05). Nevertheless, multivariate analysis showed that there was no correlation between HLA class I expression and clinical outcome. HCRT increased HLA class I expression in rectal cancer patients. However, multivariate analysis failed to show any correlation between the level of HLA class I expression and prognosis.
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