Prostaglandins, but not tumor-derived IL-10, shut down concomitant tumor-specific CTL responses during murine plasmacytoma progression.
IL-10 is assumed to be a major immunosuppressive factor produced by most B-cell tumors. The immunosuppressive role of tumor-derived IL-10 was analyzed using the MHC class II-negative BALB/c plasmacytoma ADJ-PC-5 as a model tumor. Immune monitoring of tumor-bearing mice was based on the measurement of tumor burden, tumor-specific CTL cytotoxicity and intracellular cytokine staining using FACS. ADJ-PC-5 tumor progression in syngeneic recipients is associated with strong, concomitant, tumor-specific CTL responses during early stages of tumor progression which are sufficient to cause rejection of small s.c. autologous test tumors. These initial CTL responses gradually decline during later tumor stages. Blocking of IL-10 in vivo did not abolish CTL suppression or retard tumor growth. More strikingly, application of anti-IL-10 antibodies during early tumor stages abrogated CTL induction and markedly accelerated tumor growth. In contrast to anti-IL-10 treatment, application of cyclo-oxygenase inhibitors to ADJ-PC-5 tumor-bearing mice led to enhanced tumor-specific CTL responses throughout all stages of tumor progression, paralleled by retarded tumor growth and a significantly delayed onset of suppression. Both findings contradict a dominant immunosuppressive role of IL-10 during B-cell tumor progression. Tumor-derived IL-10 must therefore be considered an immunostimulating factor, which accounts for the high immunogenicity of B-cell tumors, whereas prostaglandins, which are not produced by the tumor cells themselves, are the dominant immunosuppressors in this system.
Institute for Immunology, University of Münster, Münster, Germany.
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D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism; D002469:Cell Separation; D015232:Dinoprostone / Q000096:biosynthesis; D018450:Disease Progression; D005260:Female; D005434:Flow Cytometry; D007074:Immunoglobulin G / Q000378:metabolism; D016753:Interleukin-10 / Q000096:biosynthesis / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D010954:Plasmacytoma / Q000378:metabolism*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011453:Prostaglandins / Q000494:pharmacology*; D051381:Rats; D013154:Spleen / Q000166:cytology; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects* / Q000378:metabolism; D013997:Time Factors; D014407:Tumor Cells, Cultured
D007074:Immunoglobulin G; D011453:Prostaglandins; D016753:Interleukin-10; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone