Impaired anti-leukemic immune response in PKCtheta-deficient mice.
The cancer immunosurveillance hypothesis has found strong experimental support in recent years. It is believed that cytotoxic lymphocytes are important effectors in this process. PKCtheta 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 PKCtheta in T cell leukemia progression by inducing this disease in wild-type (wt) and PKCtheta-deficient mice with moloney-murine leukemia virus (M-MuLV). Leukemic PKCtheta(-/-) 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 PKCtheta(-/-) mice. Transfer of leukemic T cells from wt donors into PKCtheta-deficient and wt recipients induced leukemia in 100% and 40% of the mice, respectively. Interestingly, leukemic cells from PKCtheta(-/-) donors induced the disease in only 50% of the PKCtheta-deficient and 10% of the wt recipients. Intravenous injection of low numbers of EL4 cells induced tumors earlier in PKCtheta(-/-) mice. Taken together, our results show that PKCtheta is essential for the immune response to leukemia in mice and raise questions about the chronic treatment of humans with PKCtheta inhibitors.
Garaude
Johan
J
Institut de Génétique Moléculaire de Montpellier, CNRS UMR 5535, IFR 122, 1919 Route de Mende, 34293 Montpellier, France.
Kaminski
Sandra
S
Charni
Seyma
S
Aguilò
Juan Ignacio
JI
Jacquet
Chantal
C
Plays
Marc
M
Hernandez
Javier
J
Rodriguez
Fernando
F
Hipskind
Robert A
RA
Anel
Alberto
A
Villalba
Martin
M
D000818:Animals; D000831:Animals, Newborn; D007527:Isoenzymes / Q000172:deficiency* / Q000378:metabolism; D007938:Leukemia / Q000201:enzymology* / Q000276:immunology* / Q000473:pathology / Q000821:virology; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D010641:Phenotype; D011493:Protein Kinase C / Q000172:deficiency* / Q000378:metabolism; D000074121:Protein Kinase C-theta; D016019:Survival Analysis
D007527:Isoenzymes; C489593:Prkcq protein, mouse; D011493:Protein Kinase C; D000074121:Protein Kinase C-theta