Secretion of interleukin-10 from murine colon carcinoma cells suppresses systemic antitumor immunity and impairs protective immunity induced against the tumors.
Interleukin-10 (IL-10) is a T helper type 2 (Th2) cytokine that suppresses Th1-mediated, cell-mediated immune responses and reciprocally enhances antibody-mediated responses. Previous studies, however, demonstrated that forced expression of the IL-10 gene in tumor cells could unexpectedly produce antitumor effects. We then examined whether tumor-derived IL-10 could modulate systemic immune responses. Murine colon carcinoma (Colon 26) cells that were retrovirally transduced with the murine IL-10 gene (Colon 26/IL-10) were inoculated in syngeneic immunocompetent or T cell-defective nude mice. Growth of Colon 26/IL-10 tumors was augmented in immunocompetent and, to less extent, in nude mice compared with that of wild-type tumors developed in respective mice. Growth of wild-type tumors was accelerated to the same level as that of Colon 26/IL-10 tumors when wild type and Colon 26/IL-10 cells were respectively inoculated in different flanks of the same immunocompetent mice. This enhanced growth of wild-type tumors was not observed in nude mice. Immunocompetent mice that had rejected IL-2- or IL-12-secreting Colon 26 cells developed protective immunity and became completely resistant to wild-type Colon 26 cells subsequently challenged. However, some of the mice that had rejected IL-2 or IL-12 producers developed Colon 26/IL-10 tumors inoculated thereafter. The present study showed that production of IL-10 from tumor cells impaired T cell- and non-T cell-mediated systemic antitumor immunity in hosts.
Kawamura
Kiyoko
K
Division of Pathology, Chiba Cancer Center Research Institute, Japan.
Bahar
Rumana
R
Natsume
Waka
W
Sakiyama
Shigeru
S
Tagawa
Masatoshi
M
D000230:Adenocarcinoma / Q000276:immunology* / Q000378:metabolism / Q000517:prevention & control*; D000818:Animals; D000951:Antigens, Neoplasm / Q000378:metabolism; D002455:Cell Division / Q000502:physiology; D003110:Colonic Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000517:prevention & control*; D017931:DNA Primers / Q000737:chemistry; D005260:Female; D005434:Flow Cytometry; D007110:Immunity, Active; D016867:Immunocompromised Host / Q000276:immunology; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000276:immunology* / Q000378:metabolism / Q000517:prevention & control*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism* / Q000637:transplantation; D014407:Tumor Cells, Cultured / Q000637:transplantation
D000951:Antigens, Neoplasm; D017931:DNA Primers; D016753:Interleukin-10