| Title | Anti-CTLA-4 therapy in bladder cancer patients alters immune responses by increasing IFNγ production and decreasing the CD4+FOXP3+ regulatory T cells in the tumor microenvironment | ||
| Authors | Ch.I. Liakou1, A. Kamat2, D. Ng Tang1, H. Chen1, J. Sun1, Ch. Logothetis1, P. Sharma1,3
Departments of 1. Genitourinary Medical Oncology, 2. Urology and 3. Immunology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas |
||
| Citation | Liakou, C.I., Kamat, A., Tang, D.N., Cheni, H., Sun, J. et al.: Anti-CTLA-4 therapy in bladder cancer patients alters immune responses by increasing IFNγ production and decreasing the CD4+FOXP3+ regulatory T cells in the tumor microenvironment, Epitheorese Klin. Farmakol. Farmakokinet. 22(2): 217-220 (2008) | ||
| Publication Date | 23-25 May 2008 | ||
| Full Text Language | English | ||
| Order – Buy | Ηλεκτρονική Μορφή: pdf (10 €) – Digital Type: pdf (10 €)
pharmakonpress[at]pharmakonpress[.]gr |
||
| Keywords | Patients, cancer, T cells, IFNγ, CD4+FOXP3+. | ||
| Other Terms | Review article | ||
| Summary | CTLA-4 blockade is an active immunotherapeutic strategy in clinical trials for which measurable tumor responses, including durable complete responses, have been reported in some patients with metastatic disease. To date no consistent immunological changes associated either with drug administration or clinical benefit have been demonstrated. Here we present data from a neoadjuvant clinical trial demonstrating that anti-CTLA-4 therapy increases IFN-γ production by circulating CD4 T cells as compared to levels found pre-therapy or in healthy donors. Surgical specimens of tumor tissues from patients who were treated with anti-CTLA-4 antibody had similar immunological changes and furthermore decreased CD4+FOXP3+ T cells when compared with malignant tissues. These findings provide insight into the immunologic impact of CTLA-4 blockade that will be useful in understanding its mechanisms of action and optimizing its clinical development as an effective cancer immunotherapy. | ||
| References | 1. Walunas T.L., Lenschow D.J., Bakker C.Y., et al.: CTLA-4 can function as a negative regulator of T cell activation. Immunity 1: 405-413 (1994)
2. Krummel M.F., Allison J.P.: CD28 and CTLA-4 have opposing effects on the response of T cells to stimulation. J. Exp. Med. 182: 459-465 (1995) 3. Krummel M.F., Allison J.P.: CTLA-4 engagement inhibits IL-2 accumulation and cell cycle progression up activation of resting T cells. J. Exp. Med. 183: 2533-2540 (1996) 4. Leach D.R., Krummel M.F., Allison J.P.: Enhancement of antitumor immunity by CTLA-4 blockade. Science 271: 1734-1736 (1996) 5. van Elsas A., Hurwitz A.A., Allison J.P.: Combination immunotherapy of B16 melanoma using anticytotoxic T lymphocyte-associated antigen 4 (CTLA-4) and granulocyte/macrophage colony-stimulating factor (GM-CSF)-producing vaccines induces rejection of subcutaneous and metastatic tumors accompanied by autoimmune depigmentation. J. Exp. Med. 190: 355-366 (1999) 6. Korman A., Yellin M., Keler T.: Tumor immunotherapy: preclinical and clinical activity of anti-CTLA4 antibodies. Curr. Opin. Investig. Drugs 6: 582-591 (2005) 7. Sakaguchi S.: Regulatory T cells: key controllers of immunologic self-tolerance. Cell 101: 455-458 (2000) 8. Sakaguchi S.: Naturally arising Foxp3-expressing CD25+CD4+ regulatory T cells in immunological tolerance to self and non-self. Nat. Immunol. 6: 345-352 (2005) 9. Hori S., Nomura T., Sakaguchi S.: Control of regulatory T cell development by the transcription factor Foxp3. Science 299: 1057-1061 (2003) 10. Fontenot J.D., Gavin M.A., Rudensky A.Y.: Foxp3 programs the development and function of CD4+CD25+regulatory T cells. Nat. Immunol. 4: 330-6 (2003) 11. Fontenot J.D., Rasmussen J.P., Williams L.M., et al.: Regulatory T cell lineage specification by the forkhead transcription factor foxp3. Immunity 22: 329-341 (2005) 12. Quezada S.A., Peggs K.S., Curran M.A., et al.: CTLA4 blockade and GM-CSF combination immunotherapy alters the intratumoral balance of effector and regulatory T cells. J. Clin. Invest. 116: 1935-1945 (2005) 13. Dunn G.P., Koebel C.M., Schreiber R.D: Interferons, immunity and cancer immunoediting. Nat. Rev. Immunol. 6: 836-848 (2006) 14. Blankenstein T., Qin Z.: The role of IFN-gamma in tumor transplantation immunity and inhibition of chemical carcinogenesis. Curr. Opin. Immunol. 15: 148-54 (2003) 15. Trinchieri G.: Interleukin-12 and the regulation of innate resistance and adaptive immunity. Nat. Rev. Immunol. 3: 133-146 (2003) 16. Kaplan D.H., Shankaran V., Dighe S., et al.: Demonstration of an interferon gamma-dependent tumor surveillance system in immunocompetent mice. Proc. Natl. Acad. Sci. USA 95: 7556-7561 (1998) 17. Kuhns M.S., Epshteyn V., Sobel R.A., et al.: Cytotoxic T lymphocyte antigen-4 (CTLA-4) regulates the size, reactivity, and function of a primed pool of CD4+ T cells. Proc. Natl. Acad. Sci. USA 97: 12711-12716 (2000) 18. Hurwitz A.A., Sullivan T.J., Sobel R.A., et al.: Cytotoxic T lymphocyte antigen-4 (CTLA-4) limits the expansion of encephalitogenic T cells in experimental autoimmune encephalomyelitis (EAE)-resistant BALB/c mice. Proc. Natl. Acad. Sci. USA 99: 3013-3017 (2002) |
||
| Relative Papers | |||
Online ISSN 1011-6575
Άρθρα Δημοσιευμένα σε αυτό το Περιοδικό Καταχωρούνται στα:
- Chemical Abstracts
- Elsevier’s Bibliographic Databases: Scopus, EMBASE, EMBiology, Elsevier BIOBASE SCImago Journal and Country Rank Factor
Articles published in this Journal are Indexed or Abstracted in: • Chemical Abstracts • Elsevier’s Bibliographic Databases: Scopus, EMBASE, EMBiology, Elsevier BIOBASE SCImago Journal and Country Rank Factor
Συντακτικη Επιτροπή-Editorial Board
| ΕΤΗΣΙΑ ΣΥΝΔΡΟΜΗ 2008 – ANNUAL SUBSCRIPTION 2008 | |
| Γλώσσα Πλήρους Κειμένου – Full Text Language | Αγγλικά – English |
| Παραγγελία – Αγορά – Order – Buy | Ηλεκτρονική Μορφή: pdf (70 €) – Digital Type: pdf (70 €)
pharmakonpress[at]pharmakonpress[.]gr |
| Έντυπη Μορφή (70 € + έξοδα αποστολής) – Printed Type (70 € + shipping)
pharmakonpress[at]pharmakonpress[.]gr |
|