NK Cells and γδ T Cells Mediate Resistance to Polyomavirus–Induced Tumors

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.

Tumor Infiltrating Immune Cells and Outcome of Merkel Cell Carcinoma: A Population-Based Study

“…Virus-reactive CD8 þ and CD4 þ T cells have been isolated from MCPyV-positive MCCs, and MCPyV-specific T-cell responses were detected in the blood of both MCC patients and control subjects, suggesting that MCCs often develop despite the presence of T cells that are specific for MCPyV T-oncoproteins (44). Little is known about the role of the NK cells in the immune defense against MCPyV, but NK cells and gd T cells have a protective role against polyomavirus-induced tumors in some mouse models (45).…”

Immunity, inflammation, and cancer: an eternal fight between good and evil

“…NK cells recognize mouse cancer cells via ribonucleic acid export-1 (RAE-1) family ligands and human cancer via MHC class I-related genes A and B (MICA and MICB), all of which bind the NK cell-activating receptor NKG2D (84,87,88). These NKG2D ligands are upregulated during the DNA damage response and cell cycle progression via E2F transcription factors (89).…”

Heterologous Immunity and Persistent Murine Cytomegalovirus Infection

“…The MCMV glycoprotein B (gB) forward primer sequence was 5=-AGGGCTTGGAGAGGACCTACA-3=, and the reverse primer sequence was 5=-GCCCGTCGGCAGTCTAGTC-3= (70). The mouse ␤-actin forward primer sequence was 5=-CGAGGCCCA GAGCAAGAGAG-3=, and the reverse primer sequence was 5=-CGGTTGGCCTTAGGGTTCAG-3= (71). The PCR was performed on a CFX96 system (Bio-Rad) with an initial incubation at 95°C for 10 min to activate the Taq enzyme, followed by 35 amplification cycles of denaturation at 95°C for 10s and annealing and extension at 60°C for 30s.…”

“…with 5 ϫ 10 5 PFU of MCMV or given salivary gland homogenate from naive mice as controls. Memory CD8 T cells specific for GP [33][34][35][36][37][38][39][40][41] , NP 396 -404 , and GP 118 -125 , (a to d) and memory CD4 T cells specific for GP [61][62][63][64][65][66][67][68][69][70][71][72][73][74][75][76][77][78][79][80] from the spleen (e) were examined at weeks 6, 12, 23, and 48 post-MCMV infection by ICS (n ϭ 5). The complete experiment was done once, but a similar observation was made in a separate experiment in cells harvested at weeks 9 and 24 post-MCMV inoculation.…”