Differential Tumor Surveillance by Natural Killer (Nk) and Nkt Cells

By M. Smyth, K. Thia, Shayna E. A. Street, E. Cretney, J. Trapani, Masaru Taniguchi, T. Kawano, Sonja B. Pelikan, N. Crowe, D. Godfrey. Journal of Experimental Medicine, 2000

916 citations recorded by the source corpus.

Natural tumor surveillance capabilities of the host were investigated in six different mouse tumor models where endogenous interleukin (IL)-12 does or does not dictate the efficiency of the innate immune response. Gene-targeted and lymphocyte subset–depleted mice were used to establish the relative importance of natural killer (NK) and NK1.1+ T (NKT) cells in protection from tumor initiation and metastasis. In the models examined, CD3− NK cells were responsible for tumor rejection and protection from metastasis in models where control of major histocompatibility complex class I–deficient tumors was independent of IL-12. A protective role for NKT cells was only observed when tumor rejection required endogenous IL-12 activity. In particular, T cell receptor Jα281 gene-targeted mice confirmed a critical function for NKT cells in protection from spontaneous tumors initiated by the chemical carcinogen, methylcholanthrene. This is the first description of an antitumor function for NKT cells in the absence of exogenously administered potent stimulators such as IL-12 or α-galactosylceramide.

Subfields: Immunology, Oncology

View Paper: https://www.semanticscholar.org/paper/0438c876247ae01ac1911595f38fb43425766952

How researchers see this paper

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In Immunology

1. M. Smyth
2. Robert Schreiber
3. M. Karin
4. M. Kronenberg
5. S. Grivennikov
6. F. Greten
7. G. Dunn
8. Zena Werb

In Oncology

1. M. Karin
2. S. Grivennikov
3. M. Smyth
4. F. Greten
5. Robert Schreiber
6. Zena Werb
7. M. Egeblad
8. D. Pardoll

Citations in the corpus

• Cancer immunoediting: from immunosurveillance to tumor escape (2002, background): “After challenge with MCA, perforin −/− mice developed significantly more tumors compared with perforin-sufficient mice treated in the same manne”
• Inhibiting Stat3 signaling in the hematopoietic system elicits multicomponent antitumor immunity (2005, background): “As NK cells are important cytolytic effectors against tumor”
• Immunity, Inflammation, and Cancer (2010, background): “NKT cells can also be involved in surveillance of hematopoietic and chemically-induced tumors (Crowe et al., 2005; Smyth et al., 2000; Swann et al., 2009).”
• Functional significance of the perforin/granzyme cell death pathway (2002, background): “Recent studies in mice have clearly shown immunosurveillance of various spontaneous malignancie”
• Increased Susceptibility to Tumor Initiation and Metastasis in TNF-Related Apoptosis-Inducing Ligand-Deficient Mice1 (2002, background): “We and others have previously shown that MCA induction of fibrosarcomas is dose dependent and is primarily controlled by NK cells (18), NKT cells (27), and the effector molecules, pfp and IFN(28).”
• Cytokines in cancer pathogenesis and cancer therapy (2004, background): “cgi?l=51561">Il-23 , two cytokines that stimulate Ifn-γ production, and mice that lacked NKT cells, a key source of Ifn-γ, also developed more tumours in response to chemical carcinogens than normal mic”
• Perforin-Mediated Cytotoxicity Is Critical for Surveillance of Spontaneous Lymphoma (2000, background): “The lymphomas arising in pfp-deficient mice appeared to be controlled by CD81 T cells, yet clearly other innate cell types, such as NK and NKT cells, express pfp and control tumor development and metastasis (11, 24).”