How tumours escape mass destruction

Stewart, Trina J.; Abrams, Scott I.

doi:10.1038/onc.2008.268

Cited by 162 publications

(134 citation statements)

References 102 publications

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“…Resistance to immune reactions: the role of metabolism Several strategies are used by malignant cells to evade immunosurveillance, as reviewed elsewhere (Stewart and Abrams, 2008).…”

Section: Breaking Barriers: Cancer Invasion Metastasis and Cell Metamentioning

confidence: 99%

“…T lymphocytes and natural killer cells, the cytotoxic lymphocyte types responsible for triggering apoptosis of cells with defects or perceived as foreign, such as cancerous ones (Stewart and Abrams, 2008), are highly glycolytic. Their normal functions are perturbed when their MCT channels cannot efficiently extrude lactate and protons because of an excess of these molecules in the extracellular milieu (Lardner, 2001;Fischer et al, 2007).…”

Section: Breaking Barriers: Cancer Invasion Metastasis and Cell Metamentioning

confidence: 99%

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Metabolic reprogramming of the tumor

2012

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Cancer is classically considered as a genetic and, more recently, epigenetic multistep disease. Despite seminal studies in the 1920s by Warburg showing a characteristic metabolic pattern for tumors, cancer bioenergetics has often been relegated to the backwaters of cancer biology. This review aims to provide a historical account on cancer metabolism research, and to try to integrate and systematize the metabolic strategies in which cancer cells engage to overcome selective pressures during their inception and evolution. Implications of this renovated view on some common concepts and in therapeutics are also discussed.

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“…Resistance to immune reactions: the role of metabolism Several strategies are used by malignant cells to evade immunosurveillance, as reviewed elsewhere (Stewart and Abrams, 2008).…”

Section: Breaking Barriers: Cancer Invasion Metastasis and Cell Metamentioning

confidence: 99%

Section: Breaking Barriers: Cancer Invasion Metastasis and Cell Metamentioning

confidence: 99%

Metabolic reprogramming of the tumor

2012

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“…Nevertheless, multiple immunosuppressive mechanisms in tumor microenvironments can inactivate TILs, which may increase the risk of tumor recurrence after radiotherapy and chemotherapy. 4,6 A marker indicating TIL dysfunction and predicting a poor outcome after conventional treatment would help identify patients refractory nasopharyngeal carcinoma.…”

mentioning

confidence: 99%

Increase of programmed death-1-expressing intratumoral CD8 T cells predicts a poor prognosis for nasopharyngeal carcinoma

et al. 2010

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Intratumoral cytotoxic T lymphocytes are critical for controlling tumor recurrence, and programmed death-1 (PD-1) is a recognized marker of T-cell dysfunction. We analyzed this marker and its binding ligands in nasopharyngeal tumor tissue and non-cancerous nasopharyngeal control tissue to retrospectively evaluate the correlation between its expression and the post-treatment outcome of nasopharyngeal carcinoma patients. Using double immunofluorescence staining, we found that the expression of PD-1 in CD8 T cells in tumor tissue was significantly higher than in control tissue (mean: 28.4 vs 3.9%, Po0.0001). Although the expression rate of PD-1 in intratumoral CD8 cells was not associated with the other clinicopathological parameters examined, the higher expression rate in this subset of T cells significantly correlated with a poorer prognosis of overall survival, disease-free survival, and locoregional recurrence-free survival of the cancer patients (P ¼ 0.05, 0.007, and 0.004, respectively). Multivariate analysis confirmed it as an independent risk factor for death, treatment failure, and local recurrence of nasopharyngeal carcinoma. On the other hand, the expression of PD-1 in CD4 T cells and of its ligands in epithelial and stromal cells was not significantly different between tumor and control tissue, and its expression was not associated with clinical outcome of the cancer patients. We propose that PD-1 expression in CD8 cells reflects the selective suppression of cytotoxic lymphocytes in the tumor microenvironment and predicts recurrence of nasopharyngeal carcinoma after conventional therapies.

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“…Tumors use various evasion strategies to inhibit the development of antitumor immunity and avoid subsequent immune response-mediated elimination (1)(2)(3). Some of the well-recognized tumor immune evasion mechanisms include failure of tumor antigen recognition (4-6), modulation of MHC molecule expression (7,8), improper activation of antigen-presenting cells (APC; refs.…”

Section: Introductionmentioning

confidence: 99%

Reovirus Virotherapy Overrides Tumor Antigen Presentation Evasion and Promotes Protective Antitumor Immunity

Gujar

Marcato

Pan

et al. 2010

Molecular Cancer Therapeutics

105

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Tumor-associated immunosuppressive strategies, such as lack of tumor antigen recognition and failure of lymphocyte activation and homing, resist the development of tumor-specific immunity and hamper the immune response-mediated elimination of cancerous cells. In this report, we show that reovirus virotherapy overrides such a tumor immune evasion and establishes clinically meaningful antitumor immunity capable of protecting against subsequent tumor challenge. Reovirus-mediated destruction of tumor cells facilitates the recognition of tumor antigens by promoting the display of otherwise inaccessible tumorspecific immunogenic peptides on the surface of dendritic cells (DC). Furthermore, on exposure to reovirus, DCs produce IL-1α, IL-1β, IL-6, IL-12p40/70, IL-17, CD30L, eotaxin, GM-CSF, KC, MCP-1, MCP-5, M-CSF, MIG, MIP-1α, RANTES, TNF-α, VCAM-1, VSGF, CXCL-16, AXL, and MCP-2; undergo maturation; and migrate into the tumor microenvironment along with CD8 T cells. These reovirus-activated DCs also acquire the capacity to prime tumor antigen-specific transgenic T cells in vitro and intrinsic antitumor T-cell response in vivo. Further, reovirus virotherapy augments the efficacy of DC-or T cell-based anticancer immunotherapies and synergistically enhances the survival in tumor-bearing mice. Most importantly, antitumor cellular immune responses initiated during reovirus oncotherapy protect the host against subsequent tumor challenge in a reovirus-independent but antigen-dependent manner. These reovirus oncotherapy-initiated antitumor immune responses represent an anticancer therapeutic entity that can maintain a long-term cancer-free health even after discontinuation of therapy.

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How tumours escape mass destruction

Cited by 162 publications

References 102 publications

Metabolic reprogramming of the tumor

Metabolic reprogramming of the tumor

Increase of programmed death-1-expressing intratumoral CD8 T cells predicts a poor prognosis for nasopharyngeal carcinoma

Reovirus Virotherapy Overrides Tumor Antigen Presentation Evasion and Promotes Protective Antitumor Immunity

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