Anti-CTLA-4 therapy results in higher CD4(+)ICOS(hi) T cell frequency and IFN-γ levels in both nonmalignant and malignant prostate tissues Journal Article
| Authors: | Chen, H.; Liakou, C. I.; Kamat, A.; Pettaway, C.; Ward, J. F.; Tang, D. N.; Sun, J.; Jungbluth, A. A.; Troncoso, P.; Logothetis, C.; Sharma, P. |
| Article Title: | Anti-CTLA-4 therapy results in higher CD4(+)ICOS(hi) T cell frequency and IFN-γ levels in both nonmalignant and malignant prostate tissues |
| Abstract: | Cytotoxic lymphocyte antigen-4 (CTLA-4) blockade is an active immunotherapeutic strategy that is currently in clinical trials in cancer. There are several ongoing trials of anti-CTLA-4 in the metastatic setting of prostate cancer patients with reported clinical responses consisting of decreases in the prostate specific antigen (PSA) tumor marker for some patients. Immunologic markers that correlate with these clinical responses are necessary to guide further development of anti-CTLA-4 therapy in the treatment of cancer patients. We recently reported that CD4(+) inducible co- stimulator (ICOS) (hi) T cells that produce interferon-γ (IFN-γ) are increased in the peripheral blood and tumor tissues of bladder cancer patients treated with anti-CTLA-4 antibody. Here we present data from the same clinical trial in bladder cancer patients demonstrating a higher frequency of CD4 (+)ICOS(hi) T cells and IFN-γ mRNA levels in nonmalignant prostate tissues and incidental prostate tumor tissues removed at the time of radical cystoprostatectomy. Our data suggest immunologic markers that can be used to monitor prostate cancer patients who receive anti-CTLA-4 therapy and indicate that the immunologic impact of anti-CTLA-4 antibody can occur in both tumor and nonmalignant tissues. These data should be taken into consideration for evaluation of efficacy as well as immunerelated adverse events associated with anti-CTLA-4 therapy. © 2009 by The National Academy of Sciences of the USA. |
| Keywords: | clinical article; controlled study; human tissue; human cell; clinical trial; cancer patient; t cells; transcription factor foxp3; lymphocytes, tumor-infiltrating; biological marker; protein blood level; cytotoxic t lymphocyte antigen 4 antibody; interleukin 2; ipilimumab; multiple cycle treatment; transcription factor gata 3; interleukin 10; patient monitoring; drug effect; bladder cancer; prostatic neoplasms; tissue section; cytokine; th2 cell; prostate; immunotherapy; gamma interferon; messenger rna; blood sampling; rna, messenger; prostatectomy; prostate tumor; cd4+ t lymphocyte; cd4-positive t-lymphocytes; drug response; prostate adenocarcinoma; interferon-gamma; ctla-4; cd4 antigen; transcription factor t bet; cancer tissue; cd4+ inducible costimulator hi t lymphocyte; immunological monitoring; incidental finding; th1 cell; tissue level; antibodies; antigens, cd |
| Journal Title: | Proceedings of the National Academy of Sciences of the United States of America |
| Volume: | 106 |
| Issue: | 8 |
| ISSN: | 0027-8424 |
| Publisher: | National Academy of Sciences |
| Date Published: | 2009-02-24 |
| Start Page: | 2729 |
| End Page: | 2734 |
| Language: | English |
| DOI: | 10.1073/pnas.0813175106 |
| PUBMED: | 19202079 |
| PROVIDER: | scopus |
| PMCID: | PMC2650334 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 8" - "Export Date: 30 November 2010" - "CODEN: PNASA" - "Source: Scopus" |
