title: Anti-CTLA-4 therapy results in higher CD4+ICOShi T cell frequency and IFN-gamma 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-gamma (IFN-gamma) 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-gamma 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 immune-related adverse events associated with anti-CTLA-4 therapy.
authors.affiliation: Department of Genitourinary Medical Oncology, University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Hong
authors.initials: H
authors.lastname: Chen
authors.forename: Chrysoula I
authors.initials: CI
authors.lastname: Liakou
authors.forename: Ashish
authors.initials: A
authors.lastname: Kamat
authors.forename: Curtis
authors.initials: C
authors.lastname: Pettaway
authors.forename: John F
authors.initials: JF
authors.lastname: Ward
authors.forename: Derek Ng
authors.initials: DN
authors.lastname: Tang
authors.forename: Jingjing
authors.initials: J
authors.lastname: Sun
authors.forename: Achim A
authors.initials: AA
authors.lastname: Jungbluth
authors.forename: Patricia
authors.initials: P
authors.lastname: Troncoso
authors.forename: Christopher
authors.initials: C
authors.lastname: Logothetis
authors.forename: Padmanee
authors.initials: P
authors.lastname: Sharma
mesh_terms: D000906:Antibodies / Q000627:therapeutic use*; D015703:Antigens, CD / Q000187:drug effects*; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D060908:CTLA-4 Antigen; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism*; D016246:Lymphocytes, Tumor-Infiltrating / Q000166:cytology*; D008297:Male; D011467:Prostate / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000628:therapy*; D012333:RNA, Messenger / Q000235:genetics
chemical_list: D000906:Antibodies; D015703:Antigens, CD; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D012333:RNA, Messenger; D007371:Interferon-gamma