Interferons, immunity and cancer immunoediting

Dunn, Gavin P.; Koebel, Catherine M.; Schreiber, Robert D.

doi:10.1038/nri1961

Cited by 1,381 publications

(1,223 citation statements)

References 107 publications

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“…Subsets of these cells, such as CD8 + cytotoxic T‐cells and natural killer (NK) cells, may play roles in restricting tumor development and progressive growth (de Visser et al., 2006; Dunn et al., 2006). On the other hand, a growing body of research in mouse cancer models has now implicated multiple leukocyte species as causal players in cancer initiation and progression.…”

Section: Variability and Dynamics Of Stromal Cell Componentsmentioning

confidence: 99%

The biology of personalized cancer medicine: Facing individual complexities underlying hallmark capabilities

2012

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It is a time of great promise and expectation for the applications of knowledge about mechanisms of cancer toward more effective and enduring therapies for human disease. Conceptualizations such as the hallmarks of cancer are providing an organizing principle with which to distill and rationalize the abject complexities of cancer phenotypes and genotypes across the spectrum of the human disease. A countervailing reality, however, involves the variable and often transitory responses to most mechanism‐based targeted therapies, returning full circle to the complexity, arguing that the unique biology and genetics of a patient's tumor will in the future necessarily need to be incorporated into the decisions about optimal treatment strategies, the frontier of personalized cancer medicine. This perspective highlights considerations, metrics, and methods that may prove instrumental in charting the landscape of evaluating individual tumors so to better inform diagnosis, prognosis, and therapy. Integral to the consideration is remarkable heterogeneity and variability, evidently embedded in cancer cells, but likely also in the cell types composing the supportive and interactive stroma of the tumor microenvironment (e.g., leukocytes and fibroblasts), whose diversity in form, regulation, function, and abundance may prove to rival that of the cancer cells themselves. By comprehensively interrogating both parenchyma and stroma of patients' cancers with a suite of parametric tools, the promise of mechanism‐based therapy may truly be realized.

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Section: Variability and Dynamics Of Stromal Cell Componentsmentioning

confidence: 99%

The biology of personalized cancer medicine: Facing individual complexities underlying hallmark capabilities

2012

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“…However, within the tumor microenvironment, the balance between IL-12 and IL-23, which directly reflects Th1 and Th17 cell responses, is shifted toward IL-23 via activation of STAT3 [21,22]. Much attention has been paid to the finding that tumor stromal cells and tumor-associated macrophages, in part by producing IL-23, mainly contribute to the induction of cancer by promoting inflammation, whereas T cells suppress tumor development as part of the immunosurveillance system [23][24][25][26][27][28][29]. Recent research has provided evidence for the involvement of T cells in promoting tumor progression [28][29][30][31][32][33][34][35]; however, the precise effects of T cells and the cytokines they produce on tumorigenesis remain controversial.…”

Section: Introductionmentioning

confidence: 99%

“…This observation suggests that, in the case of B16 melanoma cells, IL-17 appears not to be involved in the promoting tumor growth. Resolving the mechanisms underlying these discrepancies would shed light on the regulation of anti-tumor immunity.It has been demonstrated that T cells, including abTCR 1 CD4 1 , abTCR 1 CD8 1 , and gdTCR 1 T cells, play a pivotal role in tumor immunosurveillance to eliminate tumor cells [23][24][25][26][27][28][29]. Recently, it has been shown that abTCR 1 CD4 1 and abTCR 1 CD8 1 T cells also act as tumor-promoting cells in various mouse Eur.…”

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confidence: 99%

Tumor‐infiltrating IL‐17‐producing γδ T cells support the progression of tumor by promoting angiogenesis

et al. 2010

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Based on the evidence that IL-17 is a key cytokine involved in various inflammatory diseases, we explored the critical role of IL-17-producing cd T cells for tumor development in tumor-bearing mouse model. IL-17 À/À mice exhibited a significant reduction of tumor growth, concomitantly with the decrease of vascular density at lesion area, indicating a pro-tumor property of IL-17. Among tumor-infiltrating lymphocytes (TIL), cd T cells were the major cellular source of IL-17. Analysis of TCR repertoires in TIL-cd T cells showed that circulating cd T cells, but not skin resident Vc5 1 cd T cells, produced IL-17. Neutralizing antibodies against IL-23, IL-6, and TGF-b, which were produced within the tumor microenvironment, inhibited the induction of IL-17-producing cd T cells. IL-17 production by tumor-infiltrating cd T cells was blocked by anti-cdTCR or anti-NKG2D antibodies, indicating that these ligands, expressed within the tumor microenvironment, are involved in cd T-cell activation. The IL-17-producing TIL-cd T cells exhibited reduced levels of perforin mRNA expression, but increased levels of COX-2 mRNA expression. Together, our findings support the novel concept that IL-17-producing cd T cells, generated in response to tumor microenvironment, act as tumor-promoting cells by inducing angiogenesis. IntroductionIn order to understand how tumor cells can escape immune surveillance mechanisms and thus develop anti-tumor therapies, it is critically important to investigate the mechanisms by which the immune system interacts with the tumor microenvironment. The tumor microenvironment, which is mainly composed of tumor cells, stromal cells, and tumor-infiltrating immune cells, is entirely different from noncancerous tissues. This unique microenvironment potently inhibits immune responses against tumor cells via various soluble mediators and contact-dependent mechanisms [1,2]. Previously, it was suggested that T-cell Eur. J. Immunol. 2010. 40: 1927-1937 DOI 10.1002 Cellular immune response 1927 responses within the local tumor tissue are completely inhibited. However, this concept was abandoned following the discovery of the regulatory T-cell and Th17 cell subsets, which are activated rather than suppressed in the tumor microenvironment via TGF-b and/or IL-6. Thus, the tumor microenvironment is conducive to IL-17 production. In fact, it has been shown that IL-17 is produced in human and murine tumor tissues [3][4][5]. Tumor cells promote neo-vascularization into tumor tissues through hyperproduction of angiogenic factors, which also support their own abnormal proliferation and survival [6]. It has been reported that tumor cells over-expressing IL-17 significantly promote new vessel growth into the tumor tissues [5]; however, physiological effects of IL-17 on tumor progression remain to be defined. Th17 differentiation from naïve CD4 1 T cells is regulated by TGF-b and IL-6. Proliferation, maintenance and full maturation of these cells are controlled by . Recently, it has been shown that IL-17 is produced by diverse T...

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“…9,20,21,260 Such knowledge has been instrumental for the development of a wide panel of therapeutic interventions that specifically aim at (re)establishing anticancer immunosurveillance (rather than merely causing the death of malignant cells), including peptide-based vaccination. 8,105,176,261-264 Unfortunately, it has soon become clear that the majority of immunotherapies developed so far is poorly active when employed as standalone therapeutic intervention, largely reflecting (1) natural and treatment-driven immunoediting, resulting in the selection of poorly immunogenic cancer cell populations; 115,265,266 and (2) the robust immunosuppression established by malignant cells, both locally and systemically. 267-269 In line with this notion, the vast majority of peptide-based vaccines tested in the clinic so far mediated limited, if any, therapeutic activity, despite being able to elicit tumor-targeting immune responses, at least to some degree.…”

Section: Resultsmentioning

confidence: 99%

Trial watch: Peptide-based vaccines in anticancer therapy

et al. 2018

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Peptide-based anticancer vaccination aims at stimulating an immune response against one or multiple tumor-associated antigens (TAAs) following immunization with purified, recombinant or synthetically engineered epitopes. Despite high expectations, the peptide-based vaccines that have been explored in the clinic so far had limited therapeutic activity, largely due to cancer cell-intrinsic alterations that minimize antigenicity and/or changes in the tumor microenvironment that foster immunosuppression. Several strategies have been developed to overcome such limitations, including the use of immunostimulatory adjuvants, the co-treatment with cytotoxic anticancer therapies that enable the coordinated release of damage-associated molecular patterns, and the concomitant blockade of immune checkpoints. Personalized peptide-based vaccines are also being explored for therapeutic activity in the clinic. Here, we review recent preclinical and clinical progress in the use of peptide-based vaccines as anticancer therapeutics.Abbreviations: CMP: carbohydrate-mimetic peptide; CMV: cytomegalovirus; DC: dendritic cell; FDA: Food and Drug Administration; HPV: human papillomavirus; MDS: myelodysplastic syndrome; MHP: melanoma helper vaccine; NSCLC: non-small cell lung carcinoma; ODD: orphan drug designation; PPV: personalized peptide vaccination; SLP: synthetic long peptide; TAA: tumor-associated antigen; TNA: tumor neoantigen

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Interferons, immunity and cancer immunoediting

Cited by 1,381 publications

References 107 publications

The biology of personalized cancer medicine: Facing individual complexities underlying hallmark capabilities

The biology of personalized cancer medicine: Facing individual complexities underlying hallmark capabilities

Tumor‐infiltrating IL‐17‐producing γδ T cells support the progression of tumor by promoting angiogenesis

Trial watch: Peptide-based vaccines in anticancer therapy

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