PD-1 is expressed by tumor-infiltrating immune cells and is associated with poor outcome for patients with renal cell carcinoma.
OBJECTIVE
B7-H1 is expressed by clinically aggressive forms of renal cell carcinoma (RCC) and predicts adverse outcome. B7-H1 is known to impair host immunity via interaction with the Programmed Death-1 (PD-1) receptor, which is expressed by activated T cells. Levels of immune cells expressing PD-1 (PD-1(+)) in clinical RCC tumors have not been evaluated. Thus, we tested whether immune cell PD-1 expression is observed within aggressive RCC tumors.


METHODS
Between 2000 and 2003, 267 patients underwent nephrectomy at our institution for clear cell RCC and had fresh-frozen tissue available for review. These RCC specimens were immunostained using anti-PD-1 (clone MIH4) and outcome analyses were conducted.


RESULTS
Mononuclear immune cell infiltration was observed in 136 (50.9%) specimens. PD-1(+) immune cells were present in 77 of these 136 (56.6%) tumors. In contrast, RCC tumor cells did not express PD-1. Patients with PD-1(+) immune cells were significantly more likely to harbor B7-H1(+) tumor cells (P < 0.001), larger tumors (P = 0.001), and tumors of higher nuclear grade (P = 0.001). Likewise, intratumoral PD-1(+) immune cells were associated with advanced tumor-node-metastasis stage (P = 0.005), coagulative tumor necrosis (P = 0.027), and sarcomatoid differentiation (P = 0.008). With a median follow-up of 2.9 years, 52 patients died from RCC. Univariately, patients with PD-1(+) immune cells were at significant risk of cancer-specific death compared with PD-1(-) patients (risk ratio, 2.24; P = 0.004).


CONCLUSIONS
Levels of immune cells expressing PD-1 were increased in patients with high-risk RCC tumors. Interactions between immune cell PD-1 and B7-H1 may promote cancer progression by contributing to immune dysfunction in patients with RCC.
Thompson
R Houston
RH
Department of Urology, Mayo Medical School, Mayo Clinic, Rochester, MN 55905, USA.
Dong
Haidong
H
Lohse
Christine M
CM
Leibovich
Bradley C
BC
Blute
Michael L
ML
Cheville
John C
JC
Kwon
Eugene D
ED
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000378:metabolism*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D002292:Carcinoma, Renal Cell / Q000175:diagnosis* / Q000378:metabolism / Q000401:mortality; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000401:mortality; D016131:Lymphocyte Subsets / Q000378:metabolism*; D016246:Lymphocytes, Tumor-Infiltrating / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D061026:Programmed Cell Death 1 Receptor; D016019:Survival Analysis
D015703:Antigens, CD; D051017:Apoptosis Regulatory Proteins; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor