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: 39.33). 04/2010; 29(1):235-71. DOI: 10.1146/annurev-immunol-031210-101324
Source: PubMed
ABSTRACT
The immune system can identify and destroy nascent tumor cells in a process termed cancer immunosurveillance, which functions as an important defense against cancer. Recently, data obtained from numerous investigations in mouse models of cancer and in humans with cancer offer compelling evidence that particular innate and adaptive immune cell types, effector molecules, and pathways can sometimes collectively function as extrinsic tumor-suppressor mechanisms. However, the immune system can also promote tumor progression. Together, the dual host-protective and tumor-promoting actions of immunity are referred to as cancer immunoediting. In this review, we discuss the current experimental and human clinical data supporting a cancer immunoediting process that provide the fundamental basis for further study of immunity to cancer and for the rational design of immunotherapies against cancer.

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Good review article of current theories on cancer and immunity.
Underscores the importance of the functional competence of the cells involved,
all of which are impacted by either immune aging and/or severe depletion.
Annu Rev Immunol. 2011 Apr 23;29:235-71.
Natural innate and adaptive immunity to cancer.
Vesely MD, Kershaw MH, Schreiber RD, Smyth MJ.
Department of Pathology and Immunology, Washington University School of Medicine, Missouri, USA.
Abstract - The immune system can identify and destroy nascent tumor cells in a process
termed cancer immunosurveillance, which functions as an important defense against cancer.
Recently, data obtained from numerous investigations in mouse models of cancer and in
humans with cancer offer compelling evidence that particular innate and adaptive immune
cell types, effector molecules, and pathways can sometimes collectively function as extrinsic
tumor-suppressor mechanisms. However, the immune system can also promote tumor
progression. Together, the dual host-protective and tumor-promoting actions of immunity
are referred to as cancer immunoediting. In this review, we discuss the current experimental
and human clinical data supporting a cancer immunoediting process that provide the
fundamental basis for further study of immunity to cancer and for the rational design of
immunotherapies against cancer.
http://www.annualreviews.org/doi/abs/10.1146/annurev-immunol-031210-101324?url_ver=Z39.88-
2003&rfr_dat=cr_pub%3Dpubmed&rfr_id=ori%3Arid%3Acrossref.org&journalCode=immunol
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Curr Opin Immunol. 2004 Apr;16(2):151-6.
Aging, immunity and cancer.
Hakim FT, Flomerfelt FA, Boyiadzis M, Gress RE.
Source
Experimental Transplantation and Immunology Branch, National Cancer Institute,
National Institutes of Health, 10 Center Drive, Bethesda, MD 20892-1907, USA.
Abstract
Immunosenescence, the progressive decline in immune function that develops with
age, results from cumulative alterations in critical B- and T-cell subpopulations.
Decreases in circulating memory B cells and in germinal center formation are evident
in the elderly, possibly due to diminished follicular dendritic-cell function. T-cell
dysfunction is associated with reduced thymic generation of naïve T cells, virus-
induced expansion of terminal effectors and increased levels of memory cells
producing type I and II cytokines. The diversity of the T-cell receptor repertoire is
diminished by the first two changes, and elevated type I cytokines might contribute to
the pro-inflammatory cytokine milieu present in the elderly.
http://www.sciencedirect.com/science/article/pii/S0952791504000123
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Curr Opin Immunol. 2004 Apr;16(2):151-6.
Aging, immunity and cancer.
Hakim FT, Flomerfelt FA, Boyiadzis M, Gress RE.
Source
Experimental Transplantation and Immunology Branch, National Cancer Institute,
National Institutes of Health, 10 Center Drive, Bethesda, MD 20892-1907, USA.
Abstract
Immunosenescence, the progressive decline in immune function that develops with
age, results from cumulative alterations in critical B- and T-cell subpopulations.
Decreases in circulating memory B cells and in germinal center formation are evident
in the elderly, possibly due to diminished follicular dendritic-cell function. T-cell
dysfunction is associated with reduced thymic generation of naïve T cells, virus-
induced expansion of terminal effectors and increased levels of memory cells
producing type I and II cytokines. The diversity of the T-cell receptor repertoire is
diminished by the first two changes, and elevated type I cytokines might contribute to
the pro-inflammatory cytokine milieu present in the elderly.
http://www.sciencedirect.com/science/article/pii/S0952791504000123
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    • "Because the CD8-mediated immune response was not sufficient to overcome the cancer cells in these patients, we hypothesized that the tumors developed an alternative strategy to overcome the cytotoxic activity of CD8+ T cells. Examples of immunosuppressive strategies used by tumor cells to escape immune surveillance include elevated activity of Treg cells to inhibit antitumor immune response, upregulation of CTLA-4 and PD-L1; TGF-ß production; and loss of T cell antigen presentation in the tumor (reviewed in [32]). We examined the infiltration of CD25+ regulatory T cells (Tregs) into the tumor. "
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    Preview · Article · Dec 2016 · BMC Cancer
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    • "Although the human immune system is fully capable of eliminating foreign matter and abnormal cells, cancer cells evade the immune system through various mechanisms [97] . Cancer cells can prevent T cell proliferation via upregulating toll like receptors [98], downregulating the MHC molecules and antigens presented on their surface [99] , and immunoediting immune cells in their microenvironment to promote cancer growth and survival. "
    [Show abstract] [Hide abstract] ABSTRACT: Cancer poses a serious health problem in society and is increasingly surpassing cardiovascular disease as the leading cause of mortality in the United States. Current therapeutic strategies for cancer are extreme and harsh to patients and often have limited success; the danger of cancer is intensified as it metastasizes to secondary locations such as lung, bone, and liver, posing a dire threat to patient treatment and survival. Hedgehog signaling is an important pathway for normal development. Initially identified in Drosophila, the vertebrate and mammalian equivalent of the pathway has been studied extensively for its role in cancer development and progression. As this pathway regulates key target genes involved in development, its action also allows for the modulation of the microenvironment to prepare a tumor-suitable niche by manipulating tumor cell growth, differentiation, and immune regulation, thus creating an enabling environment for progression and metastasis. In this review, we will summarize recent scientific discoveries reporting the impact of the Hedgehog signaling pathway on the tumor initiation process and metastatic cascade, shedding light on the ability of the tumor to take over a mechanism crucially intended for development and normal function.
    Preview · Article · Dec 2016 · Molecular Cancer
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    • "The parameters chosen account for tumor cell proliferation, antigen presentation, efficiency of T cell-mediated killing of melanoma cells, tumor immune escape, and the intensity of systemic immune responses induced by the immunotherapy (respectively k pmc , k atg , k iap , k iev , and k gir ). The parameter k pmc was perturbed in the interval [1, 5] . The upper bound corresponds to with a duplication time of approx. "
    [Show abstract] [Hide abstract] ABSTRACT: In this paper, we combine kinetic modelling and patient gene expression data analysis to elucidate biological mechanisms by which melanoma becomes resistant to the immune system and to immunotherapy. To this end, we systematically perturbed the parameters in a kinetic model and performed a mathematical analysis of their impact, thereby obtaining signatures associated with the emergence of phenotypes of melanoma immune sensitivity and resistance. Our phenotypic signatures were compared with published clinical data on pretreatment tumor gene expression in patients subjected to immunotherapy against metastatic melanoma. To this end, the differentially expressed genes were annotated with standard gene ontology terms and aggregated into metagenes. Our method sheds light on putative mechanisms by which melanoma may develop immunoresistance. Precisely, our results and the clinical data point to the existence of a signature of intermediate expression levels for genes related to antigen presentation that constitutes an intriguing resistance mechanism, whereby micrometastases are able to minimize the combined anti-tumor activity of complementary responses mediated by cytotoxic T cells and natural killer cells, respectively. Finally, we computationally explored the efficacy of cytokines used as low-dose co-adjuvants for the therapeutic anticancer vaccine to overcome tumor immunoresistance.
    Full-text · Article · May 2016 · Scientific Reports
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