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

癌细胞表面高表达的HLA-DR抗原与结直肠癌患者较好的预后有关，但其确切机制尚有争议。从免疫学的角度来看，干扰素-γ诱导的人类白细胞抗原-DR是CD4+T细胞识别肿瘤相关抗原所必需的。例如，正如以前报道的那样，在癌旁的正常结直肠上皮中，人类白细胞抗原-DR的表达与组织中干扰素-γ的存在有显著的一致性。另一方面，干扰素-γ通过STAT1依赖的机制在体内抑制c-myc的表达，对细胞生长、细胞周期和染色体不稳定性具有重要作用。在这项研究中，如预期的那样，癌细胞上强烈的HLA-DR阳性表达与结直肠癌患者更好的预后显著相关。原位高表达的干扰素-γ基因提示c-myc基因表达的活化程度明显降低。此外，通过多因素分析，癌细胞中的HLA-DR抗原表达以及Dukes分期是长期生存率较好的独立因素。综上所述，干扰素-γ可以诱导细胞表面的HLADR抗原，也可以抑制c-myc的原位表达，这可能是结直肠癌患者较好的长期生存所涉及的非免疫学机制。

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.