Strong HLA-DR antigen expression on cancer cells relates to better prognosis of colorectal cancer patients:: Possible involvement of c-myc suppression by interferon-γ in situ
Strong HLA-DR antigen expression on cancer cells relates to better prognosis of colorectal cancer patients:: Possible involvement of c-myc suppression by interferon-γ in situ
复制标题
DOI：
10.1111/j.1349-7006.2006.00137.x
复制
发表时间：
2006-01-01
期刊：
影响因子：
5.7
通讯作者：
Ochiai, T
中科院分区：
文献类型：
--
作者：
Matsushita, K;Takenouchi, T;Ochiai, T
癌细胞上 HLA-DR 抗原的强表达与结直肠癌患者更好的预后相关，尽管其确切机制尚存在争议。从免疫学的角度来看，由干扰素（IFN）-γ诱导的HLA-DR抗原是CD4（+）T细胞识别肿瘤相关抗原所必需的。例如，如之前报道的，紧邻癌症的正常结直肠上皮中 HLA-DR 抗原的表达与组织中 IFN-γ mRNA 的存在显着一致。另一方面，IFN-γ已被揭示通过stat1依赖性机制在体内抑制c-myc表达，这对于细胞生长、细胞周期和染色体不稳定很重要。在本研究中，癌细胞上 HLA-DR 的强阳性表达与结直肠癌患者更好的预后显着相关。原位高 IFN-γ mRNA 表达表明 c-myc mRNA 表达的激活显着减少。此外，通过多变量分析，癌细胞中的 HLA-DR 抗原表达以及 Dukes 分期是更好的长期生存的独立因素。综上所述，IFN-γ可在细胞表面诱导HLA-DR抗原，也可原位抑制c-myc表达，并且是一种可能的非免疫机制，有助于结直肠癌患者更好的长期生存。
Strong HLA-DR antigen expression on cancer cells relates to better prognosis of colorectal cancer patients, although the precise mechanism is controversial. From an immunological point of view, HLA-DR antigen, induced by interferon (IFN)-gamma, 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-gamma mRNA in the tissue. From another aspect, IFN-gamma has been revealed to suppress c-myc expression in vivo through a stat1-dependent mechanism, which is important for cell growth, cell cycle and chromosome instability. In the present study, strong HLA-DR-positive expression on cancer cells was significantly related to better prognosis for colorectal cancer patients. High IFN-gamma 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-gamma, which induces HLA-DR antigens on the cell surface, also suppresses c-myc expression in situ, and is a possible non-immunological mechanism involved in the better long-term survival of colorectal cancer patients.