We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
An immune-active tumor microenvironment favors clinical response to ipilimumab.
- Authors
Ji, Rui-Ru; Chasalow, Scott; Wang, Lisu; Hamid, Omid; Schmidt, Henrik; Cogswell, John; Alaparthy, Suresh; Berman, David; Jure-Kunkel, Maria; Siemers, Nathan; Jackson, Jeffrey; Shahabi, Vafa
- Abstract
Purpose: Ipilimumab, a fully human monoclonal antibody specific to CTLA-4, has been shown to improve overall survival in metastatic melanoma patients. As a consequence of CTLA-4 blockade, ipilimumab treatment is associated with proliferation and activation of peripheral T cells. To better understand various tumor-associated components that may influence the clinical outcome of ipilimumab treatment, gene expression profiles of tumors from patients treated with ipilimumab were characterized. Experimental design: Gene expression profiling was performed on tumor biopsies collected from 45 melanoma patients before and 3 weeks after the start of treatment in a phase II clinical trial. Results: Analysis of pre-treatment tumors indicated that patients with high baseline expression levels of immune-related genes were more likely to respond favorably to ipilimumab. Furthermore, ipilimumab appeared to induce two major changes in tumors from patients who exhibited clinical activity: genes involved in immune response showed increased expression, whereas expression of genes for melanoma-specific antigens and genes involved in cell proliferation decreased. These changes were associated with the total lymphocyte infiltrate in tumors, and there was a suggestion of association with prolonged overall survival in these patients. Many IFN-γ-inducible genes and Th1-associated markers showed increased expression after ipilimumab treatment, suggesting an accumulation of this particular type of T cell at the tumor sites, which might play an important role in mediating the antitumor activity of ipilimumab. Conclusions: These results support the proposed mechanism of action of ipilimumab, suggesting that cell-mediated immune responses play an important role in the antitumor activity of ipilimumab.
- Subjects
MELANOMA immunotherapy; IPILIMUMAB; CANCER immunology; MONOCLONAL antibodies; T cells; CELL proliferation; TREATMENT effectiveness; GENE expression
- Publication
Cancer Immunology, Immunotherapy, 2012, Vol 61, Issue 7, p1019
- ISSN
0340-7004
- Publication type
Article
- DOI
10.1007/s00262-011-1172-6