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Strong HLA-DR antigen expression on cancer cells relates to better prognosis of colorectal cancer patients : Possible involvement of c-myc suppression by IFN-γ in situ

癌细胞上 HLA-DR 抗原的强表达与结直肠癌患者的更好预后相关：可能与 IFN-γ 原位抑制 c-myc 相关

基本信息

批准号：
18591454
负责人：
NISHIMORI Takanori
金额：
$ 2.57万
依托单位：
Chiba University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18591454/
关键词：
Human Leukocyte Antigen HLA-DR antigen cytokine c-myc gene helper T-cell

项目摘要

Strong HLA-DR antigen expression on cancer cells relates to better prognosis of colorectal cancer patients, although the precise mechanism is controversial. From an immunologic point of view, HLA-DR antigen, induced by IFN-γ, is required for tumor-associated antigen recognition by CD4+ T cells. For instance, as reported previously, the expression of HLA-DR antigen in normal colorectal epithelium immediately adjacent to cancer coincided significantly with the existence of IFN-γ mRNA in the tissue. From another aspect, IFN-γ has been revealed to suppress c-myc expression in vivo through stat1-dependent mechanism, which is important for cell growth, cell cycle, and chromosome instability. In this study, strong HLA-DR-positive expression on cancer cells, as expectedly, was significantly related to better prognosis of colorectal cancer patients. High IFN-γ mRNA expression in situ indicated significantly less activation of c-myc mRNA expression. Further, HLA-DR antigen expression in cancer cells, as well as Dukes stages, was an independent factor for better long-term survival by multivariate analysis. Taken together, IFN-γ, which induces HLA-DR antigens on the cell surface, also suppresses c-myc expression in situ, and is a possible non-immunologic mechanism involved in the better long-term survival of colorectal cancer patients.

HLA-DR抗原在大肠癌细胞上的高表达与大肠癌患者的良好预后有关，尽管其确切机制存在争议。从免疫学的角度来看，IFN-γ诱导的HLA-DR抗原是CD 4 + T细胞识别肿瘤相关抗原所必需的。例如，如前所述，在癌旁正常结直肠上皮中HLA-DR抗原的表达与组织中IFN-γ mRNA的存在显著一致。另一方面，IFN-γ在体内通过stat 1依赖性机制抑制c-myc表达，这对细胞生长、细胞周期和染色体不稳定性很重要。在本研究中，癌细胞上HLA-DR的强阳性表达，作为一种辅助手段，与结直肠癌患者的预后较好显著相关。原位高IFN-γ mRNA表达表明c-myc mRNA表达的激活明显减弱。此外，通过多变量分析，癌细胞中HLA-DR抗原表达以及Dukes分期是更好长期生存的独立因素。总之，IFN-γ诱导细胞表面的HLA-DR抗原，也抑制c-myc原位表达，并且是涉及结直肠癌患者更好的长期存活的可能的非免疫学机制。