title: Strong HLA-DR antigen expression on cancer cells relates to better prognosis of colorectal cancer patients: Possible involvement of c-myc suppression by interferon-gamma in situ.
abstract: 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.
authors.affiliation: Department of Frontier Surgery (M9), Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuoh-ku, Chiba 260-8677, Japan. kmatsu@faculty.chiba-u.jp
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Matsushita
authors.forename: Toshinao
authors.initials: T
authors.lastname: Takenouchi
authors.forename: Hideaki
authors.initials: H
authors.lastname: Shimada
authors.forename: Takeshi
authors.initials: T
authors.lastname: Tomonaga
authors.forename: Hideki
authors.initials: H
authors.lastname: Hayashi
authors.forename: Ayumi
authors.initials: A
authors.lastname: Shioya
authors.forename: Aki
authors.initials: A
authors.lastname: Komatsu
authors.forename: Hisahiro
authors.initials: H
authors.lastname: Matsubara
authors.forename: Takenori
authors.initials: T
authors.lastname: Ochiai
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D004848:Epithelium / Q000378:metabolism / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006684:HLA-DR Antigens / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011379:Prognosis; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D015996:Survival Rate; D013997:Time Factors
chemical_list: D006684:HLA-DR Antigens; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D007371:Interferon-gamma