UroToday - The importance of the B7 family of proteins as negative regulators of the immune response and markers of virulence in RCC was demonstrated in these three studies out of the Kwon laboratory at Mayo Clinic.
B7-H1 was again reported on and shown to be an independent prognostic variable predictive of cancer progression (RR 3.46) and death from RCC (RR 4.13). Programmed Death 1 (PD-1), the receptor for B7-H1 expressed by T-cells and a negative regulator of immunity, was also studied. PD-1 is not expressed by tumor cells but rather by tumor infiltrating lymphocytes.
Lymphocyte infiltration was noted in 142/284 nephrectomy specimens. Of these 56.6% stained positive for PD-1. PD-1 lymphocyte expression was associated with a greater risk of cancer specific death (RR 2.25).
Those patients that fared the worst in this study, not surprisingly, were those that had B7-H1 positive tumors, and PD-1 positive infiltrating lymphocytes. Finally, B7-H4 was introduced as another member of the B7 protein family associated with immune dysfunction and increased tumor virulence in RCC.
Like B7-H1, tumor expression of B7-H4 was associated with a significantly increased risk of dying from RCC (RR2.57). In fact, the worst prognosis was noted in patient's tumors that expressed both B7-H1 and H4 (36.3% of those studied), which had a 3 fold increased risk of dying from their disease.
These studies emphasize the importance of the B7 protein family as negative immunoregulators in RCC that adversely affect outcome and seem to be encouraging targets for therapeutic development.
By Christopher G. Wood, MD
Abstracts 385
Thompson, RH, et al. , Rochester, MN
Related Abstracts:
TUMOR B7-H1 IS ASSOCIATED WITH POOR PROGNOSIS IN RENAL CELL CARCINOMA PATIENTS WITH LONG TERM FOLLOW-UP
Abstracts 386
Thompson, RH, et al. , Rochester MN
THE IMMUNOMODULATORY PROTEIN B7-H4 EXPRESSION IN RENAL CELL CARCINOMA PATIENTS: A STRONG PREDICTOR OF CANCER PROGRESSION AND SURVIVAL
Abstract 387
Krambeck, AE et al. , Rochester, MN
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