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: Kazuyuki Matsushita, Toshinao Takenouchi, Hideaki Shimada, Takeshi Tomonaga, Hideki Hayashi, Ayumi Shioya, Aki Komatsu, Hisahiro Matsubara, Takenori Ochiai
• Journal: Cancer science (Cancer Sci) Vol. 97 Issue 1 Pg. 57-63 (Jan 2006) ISSN: 1347-9032 [Print] England
• PMID: 16367922 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: (Cancer Sci 2006; 97: 57- 63).

Chemical References

• HLA-DR Antigens
• Proto-Oncogene Proteins c-myc
• RNA, Messenger
• Interferon-gamma

Topics

• Adult
• Aged
• Aged, 80 and over
• Cell Line, Tumor
• Colorectal Neoplasms (diagnosis, genetics, metabolism, pathology)
• Epithelium (metabolism, pathology)
• Female
• Gene Expression Regulation, Neoplastic
• HLA-DR Antigens (genetics, metabolism)
• Humans
• Interferon-gamma (genetics, metabolism)
• Male
• Middle Aged
• Neoplasm Metastasis
• Prognosis
• Proto-Oncogene Proteins c-myc (genetics, metabolism)
• RNA, Messenger (genetics)
• Survival Rate
• Time Factors