Résumé
The cancer immunosurveillance hypothesis has found strong experimental support in recent years. It is believed that cytotoxic lymphocytes are important effectors in this process. PKCθ plays an essential role in proliferation, activation and survival of these cells, but also proliferation and survival of leukemic T cells. In light of this, we tested the role of PKCθ in T cell leukemia progression by inducing this disease in wild-type (
wt) and PKCθ-deficient mice with moloney-murine leukemia virus (M-MuLV). Leukemic
PKCθ
−/− and wild-type (
wt) mice showed the same profile of leukemic cell types, similar spleen and thymus sizes and comparable hematocrits. In contrast, disease incidence was higher and disease onset more rapid in
PKCθ
−/− mice. Transfer of leukemic T cells from
wt donors into PKCθ-deficient and
wt recipients induced leukemia in 100% and 40% of the mice, respectively. Interestingly, leukemic cells from
PKCθ
−/− donors induced the disease in only 50% of the PKCθ-deficient and 10% of the
wt recipients. Intravenous injection of low numbers of EL4 cells induced tumors earlier in
PKCθ
−/− mice. Taken together, our results show that PKCθ is essential for the immune response to leukemia in mice and raise questions about the chronic treatment of humans with PKCθ inhibitors.