Renal cell carcinoma induces prostaglandin E2 and T-helper type 2 cytokine production in peripheral blood mononuclear cells.
BACKGROUND
Patients with renal cell carcinoma (RCC) do not develop an effective antitumor immune response, despite significant infiltration by lymphocytes. Tumor production of immunosuppressive factors may account for this failure. The object of this study was to investigate the production of immunosuppressive mediators, especially prostaglandin E(2) (PGE(2)), by RCC.


METHODS
Peripheral blood mononuclear cells (PBMC) were cocultured with conditioned medium (CM) from human RCC cell lines in the presence or absence of NS-398, a selective cyclooxygenase 2 (COX-2) inhibitor. Supernatants were analyzed for levels of PGE(2), interleukin (IL)-10, IL-6, IL-2, interferon-gamma, and IL-12. The effects of RCC CM on PBMC proliferation were also examined. The expression of basal and stimulated COX-2 messenger RNA in the cell lines was assessed by reverse transcriptase-polymerase chain reaction.


RESULTS
RCC CM significantly increased PGE(2) production by PBMC. T-helper type 2 (Th2) cytokine production was also significantly increased. Th1 cytokines were unchanged or decreased. RCC CM increased proliferation of PBMC. Coculture with NS-398 reduced PBMC PGE(2) production to below control levels and significantly decreased IL-6 production and PBMC proliferation. NS-398 had no effect on cellular production of IL-10 or Th1 cytokines.


CONCLUSIONS
Human RCC inhibits the host antitumor immune response by promoting PGE(2) production and Th2 cytokines in PBMC. Selective inhibition of COX-2 may have a role in abrogating this effect.
Smyth
Gordon P
GP
Department of Surgery, Weill Medical College of Cornell University/New York Presbyterian Hospital, New York, New York, USA.
Stapleton
Philip P
PP
Barden
Catherine B
CB
Mestre
Juan R
JR
Freeman
Tracy A
TA
Duff
Michael D
MD
Maddali
Sirish
S
Yan
Zhaoping
Z
Daly
John M
JM
D002292:Carcinoma, Renal Cell / Q000276:immunology*; D018920:Coculture Techniques; D017077:Culture Media, Conditioned; D016207:Cytokines / Q000096:biosynthesis*; D015232:Dinoprostone / Q000096:biosynthesis*; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D007680:Kidney Neoplasms / Q000276:immunology*; D012333:RNA, Messenger / Q000096:biosynthesis; D018418:Th2 Cells / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D017077:Culture Media, Conditioned; D016207:Cytokines; D007376:Interleukin-2; D015850:Interleukin-6; D012333:RNA, Messenger; D015232:Dinoprostone