Article
Natural innate and adaptive immunity to cancer.
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Annual Review of Immunology (impact factor:
52.76).
04/2010;
29:235-71.
DOI:10.1146/annurev-immunol-031210-101324
pp.235-71
Source: PubMed
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Citations (0)
- Cited In (10)
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Article: Immune dependent and independent anti-tumor activity of GM-CSF aberrantly expressed by mouse and human colorectal tumors.
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ABSTRACT: Granulocyte-macrophage colony-stimulating factor (GM-CSF/CSF2) is a cytokine produced in the hematological compartment that may enhance anti-tumor immune responses, mainly by activation of dendritic cells. Here we show that more than a third of human colorectal tumors exhibit aberrant DNA demethylation of the GM-CSF promoter and overexpress the cytokine. Mouse engraftment experiments with autologous and homologous colon tumors engineered to repress the ectopic secretion of GM-CSF revealed the tumor-secreted GM-CSF to have an immune-associated antitumor effect. Unexpectedly, an immune-independent anti-tumor effect was observed that depended on the ectopic expression of GM-CSF receptor subunits by tumors. Cancer cells expressing GM-CSF and its receptor did not develop into tumors when autografted into immunocompetent mice. Similarly, 100% of the patients with human colon tumors that overexpressed GM-CSF and its receptor subunits survived at least 5 years after diagnosis. These data suggest that expression of GM-CSF and its receptor subunits by colon tumors may be a useful marker for prognosis as well as for patient stratification in cancer immunotherapy.Cancer Research 10/2012; · 7.86 Impact Factor -
Article: Interactions between the tumor suppressor p53 and immune responses.
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ABSTRACT: PURPOSE OF REVIEW: The p53 tumor suppressor is a master regulator of antitumor defenses through its control of growth arrest, senescence and apoptosis. In recent years, p53 regulation was found to extend to a variety of biological processes including autophagy, fertility, metabolism and immune responses. Here, we focus on the role of p53 in the immune system. We explore the relationship between p53 and the innate immune response with particular emphasis on the Toll-like receptor (TLR) pathway and implications for cancer therapy. RECENT FINDINGS: Numerous studies have shown that the immune system, especially innate immunity, has a critical role in tumor development. It appears that p53 can influence innate immune responses as part of its tumor suppressor activities and recent work suggests that the complete set of innate immune TLR genes are responsive to chromosomal stress and the transcriptional network regulated by p53. Activation of p53 by common antitumor agents results in p53 dependent regulation of expression of most TLR genes in human primary and cancer cell lines, resulting in modulation of TLR downstream responses to cognate ligands. In addition several tumor-associated p53 mutants can also affect TLR gene expression. These observations together with the discovery of other immune-related p53 target genes provide new insights into the relationship between p53 and immunity and suggest approaches that might be useful in cancer therapies. SUMMARY: The tumor suppressor p53 can modulate innate immune gene responses in response to factors that can activate p53. This is expected to provide new opportunities in cancer diagnosis and in chemotherapeutic strategies that employ specific TLR agonists or antagonists that target the TLR pathway.Current opinion in oncology 11/2012; · 4.09 Impact Factor -
Article: Human Hemato-Lymphoid System Mice: Current Use and Future Potential for Medicine.
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ABSTRACT: To directly study complex human hemato-lymphoid system physiology and respective system-associated diseases in vivo, human-to-mouse xenotransplantation models for human blood and blood-forming cells and organs have been developed over the past three decades.Wehere review the fundamental requirements and the remarkable progress made over the past few years in improving these systems, the current major achievements reached by use of these models, and the future challenges to more closely model and study human health and disease and to achieve predictive preclinical testing of both prevention measures and potential new therapies. Expected final online publication date for the Annual Review of Immunology Volume 31 is March 19, 2013. Please see http://www.annualreviews.org/catalog/pubdates.aspx for revised estimates.Annual Review of Immunology 01/2013; · 52.76 Impact Factor
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Keywords
adaptive immune cell types
cancer immunoediting
cancer immunoediting process
cancer immunosurveillance
cancer offer compelling evidence
current experimental
defense
extrinsic tumor-suppressor mechanisms
humans
immune system
nascent tumor cells
numerous investigations
particular innate
pathways
rational design
tumor-promoting actions
