Format

Send to

Choose Destination
Immunotherapy. 2009 Jan;1(1):129-39. doi: 10.2217/1750743X.1.1.129.

Inhibitors of B7-CD28 costimulation in urologic malignancies.

Author information

1
Memorial Sloan-Kettering Cancer Center, NY, USA.

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.

KEYWORDS:

lymphocyte activation; prostatic neoplasm; regulatory T lymphocyte; renal cell carcinoma; urinary bladder neoplasm

PMID:
20445772
PMCID:
PMC2864044
DOI:
10.2217/1750743X.1.1.129
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Atypon Icon for PubMed Central
Loading ...
Support Center