B7-H3, an immune molecule that plays a critical role in the development of prostate cancer, could be a potential marker for predicting the cancer recurrence and progression after surgery, according to a research article published in the August 2007 issue of Cancer Research.
Roth and fellow researchers from the Mayo Clinic have evaluated the expression of B7-H3 protein in tissue samples obtained from 338 prostate cancer patients who underwent radical prostatectomy between 1995 and 1998. They found that patients with the highest levels of protein expression were more prone to prostate cancer progression compared to patients with lower levels (risk ratio, 4.42; P < 0.001). Scientists speculate that B7- H3 protects the malignant cells from the attack of immune cells.
Suh et al (Nature Immunology, 2003) investigated the invivo function of B7-H3 in mice models and concluded that B7-H3 is a negative regulator of T helper type1-mediated immune responses. Contrary to these findings, Sun et al (Gene Therapy, 2003) suggested that the B7-H3 molecule, which demonstrates antitumor activity, including the ability to stimulate Th1 and cytotoxic T-cell responses, could be a potent therapeutic tool against cancer. They investigated the antitumor activity of the molecule by injecting B7-H3 expression plasmids into mice tumors, and noted that the mice models had a complete regression of over 50% of the tumors.
In a recent issue of the Journal of The National Cancer Institute, Fall et al reported that the Prostate Specific Antigen (PSA) blood test is an inaccurate tool for predicting lethal prostate cancer in patients placed under watchful waiting. Wang et al (New England Journal of Medicine, 2005) used a phage-peptide detector to evaluate a set of serum samples obtained from both prostate cancer patients and control groups. The new biomarker demonstrated 88.2% specificity and 81.6% sensitivity in distinguishing between the group with prostate cancer and the control group, and the team concluded that it is a better diagnostic marker than conventional PSA testing in diagnosing prostate cancer.
Prostate cancer is the second most common cancer in males, after lung cancer. Worldwide, around 670,000 men are diagnosed with prostate cancer every year. Although further studies are needed to understand how the B7-H3 molecule affects the immune system, and to identify if any mutation of the gene coding for B7-H3 is involved in the anti-immune activity, scientists hope that the new discovery will help to develop more effective diagnostic, prognostic, and even therapeutic tools against prostate cancer.
References
1. Roth TJ, Sheinin Y, Lohse CM, et al. B7-h3 ligand expression by prostate cancer: a novel marker of prognosis and potential target for therapy. Cancer Res. 2007 Aug 15;67(16):7893-900. Epub 2007 Aug 8.
2. Suh W-K, Gajewska BU, Okada H, et al. The B7 family member B7-H3 preferentially down-regulates T helper type 1−mediated immune responses. Nature Immunology. 2003 August. 4, 899–906.
3. Sun X, Vale M, Leung E, et al. Mouse B7-H3 induces antitumor immunity. Gene Therapy. 2003 September; 10(20): 1728-1734.
4. Fall K, Garmo H, Andren O, et al. Prostate-Specific Antigen Levels as a Predictor of Lethal Prostate Cancer. Journal of the National Cancer Institute. 2007 April; 99(7): 526-532.
5. Wang X, Yu J, Sreekumar A, et al. Autoantibody signatures in prostate cancer. N Engl J Med. 2005 Sep 22;353(12):1224-35.
