Tumor-induced IL10 production in vivo suppresses the development of delayed type hypersensitivity (DTH) to tumor associated antigens (Meeting abstract).

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Tumor-induced IL10 production in vivo suppresses the development of delayed type hypersensitivity (DTH) to tumor associated antigens (Meeting abstract).

Proc Annu Meet Am Assoc Cancer Res; 38:A2397 1997. Unique Identifier : AIDSLINE ICDB/98639397
Maguire HC Jr; Ketcha KA; Halak BK; Holmes KL; Lattime EC; Thomas Jefferson University, Philadelphia, PA 19107

Abstract: IL10 inhibits the induction of cell-mediated immunity (CMI) by suppressing antigen presentation to TH1 cells. We have published that biopsy specimens from patients with melanoma and bladder carcinoma express IL10 mRNA and secrete IL10 protein. To assess the role of IL10 in the development of CMI to tumor antigens, we have studied the MB49 bladder carcinoma. MB49 grows progressively in female C57BL/6 (B6) mice and expresses the male-associated HY antigen (susceptible to HY-specific CTL, lack of growth in HY-immune recipients). In vivo growth of MB49 induces IL10 mRNA expression (MB49 expresses neither IL10 mRNA nor protein). Female B6 mice primed to male spleen develop strong DTH to HY while priming with the HY-expressing MB49 fails to induce a DTH response in vivo. Administration of anti-IL10 antibody prior to tumor inoculation allows the generation of HY DTH demonstrating that the in vivo production of IL10 suppresses the CMI response to the tumor-associated HY antigen. In vitro, splenic T cells from male spleen primed but not MB49 primed female mice demonstrate an HY-specific TH1 (IFNg producing) response. As with DTH, pretreatment of mice with anti-IL10 prior to MB49 growth allows the generation of an IFNg response to HY. The above studies demonstrate that tumor-induced IL10 production, as we and others have shown to be present in patients with a number of tumor types, suppresses the development of CMI to tumor-associated antigens thus supporting further study into the manipulation of IL10 activity in the immunotherapy of tumors.

Keywords: Animal Antigens, Neoplasm/*IMMUNOLOGY Bladder Neoplasms/*IMMUNOLOGY/PATHOLOGY Cell Division Female *Hypersensitivity, Delayed Interleukin-10/*BIOSYNTHESIS/GENETICS Male Mice Mice, Inbred C57BL Th1 Cells/IMMUNOLOGY ABSTRACT
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M9820750

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