Inhibitors of B7-CD28 costimulation in urologic malignancies

R. Houston Thompson, Eugene D. Kwon, James P. Allison

Research output: Contribution to journalReview article

12 Scopus citations

Abstract

T-cell costimulatory molecules deliver positive or negative signals to govern the ultimate fate of immune responses. These ligands and receptors that negatively costimulate T cells (including cytotoxic T-lymphocyte antigen [CTLA]-4, B7-H1, programmed death [PD]-1, B7-H3 and B7x) have received significant interest recently owing to their proposed ability to form a molecular shield for tumor cells. CTLA-4 represents the most extensively studied receptor in the costimulatory pathway and functions as a potent inhibitor of T-cell-mediated immunity. Clinical trials with anti-CTLA-4 are ongoing, although numerous objective responses have been observed in heavily pretreated patients, albeit with autoimmune side effects. In renal cell carcinoma, B7-H1, PD-1 and B7x have been observed to be expressed on tumor cells or infiltrating lymphocytes and are individually associated with adverse pathologic features and poor clinical outcome. In prostate cancer, B7-H3 and B7x immunostaining intensity correlate with disease spread, clinical cancer recurrence and cancer-specific death. External validation and prospective studies are now needed to confirm these findings, while further development of humanized monoclonal antibodies, similar to the experience with anti-CTLA-4, are underway. Herein, we review the B7-CD28 family as it applies to urologic malignancies.

Original languageEnglish (US)
Pages (from-to)129-139
Number of pages11
JournalImmunotherapy
Volume1
Issue number1
DOIs
StatePublished - 2009

Keywords

  • Lymphocyte activation
  • Prostatic neoplasm
  • Regulatory T lymphocyte
  • Renal cell carcinoma
  • Urinary bladder neoplasm

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Oncology

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