Abstract
NK and γδ T cells can eliminate tumor cells in many experimental models, but their effect on the development of tumors caused by virus infections in vivo is not known. Polyomavirus (PyV) induces tumors in neonatally infected mice of susceptible strains and in adult mice with certain immune deficiencies, and CD8+ αβ T cells are regarded as the main effectors in anti-tumor immunity. Here we report that adult TCRβ knockout (KO) mice that lack αβ but have γδ T cells remain tumor-free after PyV infection, whereas TCRβ×δ KO mice that lack all T cells develop tumors. In addition, E26 mice, which lack NK and T cells, develop the tumors earlier than TCRβ×δ KO mice. These observations implicate γδ T and NK cells in the resistance to PyV-induced tumors. Cell lines established from PyV-induced tumors activate NK and γδ T cells both in culture and in vivo and express Rae-1, an NKG2D ligand. Moreover, these PyV tumor cells are killed by NK cells in vitro, and this cytotoxicity is prevented by treatment with NKG2D-blocking antibodies. Our findings demonstrate a protective role for NK and γδ T cells against naturally occurring virus-induced tumors and suggest the involvement of NKG2D-mediated mechanisms.
Highlights
Virus-induced tumors mostly develop in immune-compromised hosts, suggesting that the immune system provides protection against the induction and/or progression of these tumors
The lack of a wide spectrum of tumors in these mice is similar to findings previously reported for B6/b2m KO mice infected as adults [22]
There was an earlier appearance of tumors in E26 mice than in TCRb6d KO mice (Fig. 1C), suggesting that NK cells may contribute to tumor resistance and delay the onset of tumor formation
Summary
Virus-induced tumors mostly develop in immune-compromised hosts, suggesting that the immune system provides protection against the induction and/or progression of these tumors. A growing body of experimental evidence suggests that tumor cells can be recognized and eliminated by NK cells and cd T cells. In a variety of human cancers such as lung, colon and renal cell carcinomas NK cells and cd T cells can be found among tumor infiltrating lymphocytes (TIL) [1,2,3,4]. NK cell infiltration of tumors was noted to be associated with improved prognosis in some human cancers [4,5,6]. Implanted syngeneic tumors, including those induced by tumor viruses, grow more aggressively in mice if no functional NK cells are present [7]. Evidence that NK and cd T cells can control the formation and progression of naturally occurring virus-induced tumors is lacking
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