IL-10 expression by CT26 colon carcinoma cells inhibits their malignant phenotype and induces a T cell-mediated tumor rejection in the context of a systemic Th2 response.
In spite of the evidence that IL-10 has Th1-immunosuppressive and anti-inflammatory effects, it has been shown that IL-10 may reduce the tumorigenic capacity of certain tumor cell types. In order to characterize the responses elicited by IL-10, we explored the effect of transducing murine CT26 colon carcinoma cells with a recombinant retrovirus expressing mIL-10. IL-10 gene transfer of CT26 cells had no effect on tumor cell growth on plastic surface but inhibited the anchorage-independent growth capacity of tumor cells and their metastatic potential as assessed by their invasive and migration ability. Expression of IL-10 also elicited an antitumor immune response involving both CD4+ and CD8+ T cells. Assessment of the immune status of the animals demonstrated that mice injected with CT26-IL10 cells showed prevalence of a systemic and tumor-specific Th2 response. Spleen cells obtained from these mice showed an increased production of IL-4 and no changes in IFNgamma levels, characteristic of a Th2 response. These results demonstrate that IL-10 affects CT26 tumor cell growth by both inhibiting the malignant phenotype and by recruiting and activating a T cell-mediated antitumor response. This T cell response occurs in the context of a shift towards a Th2 response.
Adris
S
S
Gene Therapy Laboratory, Instituto de Investigaciones Bioquímicas Fundación Campomar, CONICET, FCEYN, Universidad de Buenos Aires, Argentina.
Klein
S
S
Jasnis
M
M
Chuluyan
E
E
Ledda
M
M
Bravo
A
A
Carbone
C
C
Chernajovsky
Y
Y
Podhajcer
O
O
D000704:Analysis of Variance; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003110:Colonic Neoplasms / Q000276:immunology / Q000628:therapy*; D005434:Flow Cytometry; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007371:Interferon-gamma / Q000276:immunology; D016753:Interleukin-10 / Q000235:genetics* / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009361:Neoplasm Invasiveness; D012190:Retroviridae / Q000235:genetics; D013154:Spleen / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology*; D014407:Tumor Cells, Cultured
D007074:Immunoglobulin G; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma