Toll-like receptors and immune regulation: implications for cancer therapy

Wang, Rongfu; Miyahara, Yoshihiro; Wang, Helen Yicheng

doi:10.1038/sj.onc.1210906

Cited by 133 publications

(97 citation statements)

References 109 publications

(124 reference statements)

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“…[30][31][32][33][34] The CD28 costimulatory pathway plays an important role in antitumor responses. Immunodeficient mice have been cured of established human and rodent tumors when treated with anti-CD28 antibodies.…”

Section: Regulatory T Cells In Endometrial Cancer/chang Et Almentioning

confidence: 99%

“…37 Therefore, enhanced recruitment of antitumor effector T lymphocytes to tumor tissue, in addition to inhibition of local regulatory T cells, may be an ideal target for improving cancer immunotherapy. [30][31][32][33][34][38][39][40] Strategies aimed at depletion/functional inhibition of these cells by molecular targeting must maintain a critical balance between tumor immunity and self-tolerance. 34,[41][42][43][44] These immunomodulation pathways may therefore have potential applications in forthcoming treatments of cancer.…”

Section: Regulatory T Cells In Endometrial Cancer/chang Et Almentioning

confidence: 99%

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Clinical significance of regulatory T cells and CD8+ effector populations in patients with human endometrial carcinoma

Chang

Huang

et al. 2010

Cancer

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BACKGROUND: A study was carried out to determine the functional attributes of CD4 þ CD25 þ regulatory T cells in cancer progression by suppressing antitumor immunity. METHODS: Triple-color flow cytometry was used to study the phenotype expression of CD4 þ CD25 þ regulatory T cells and CD8 þ T cells in the peripheral blood lymphocytes (PBLs) and tumor-infiltrating lymphocytes (TILs) of 57 cases of stage I to IV endometrial carcinoma. The expression of T cell subsets was correlated with clinical prognostic parameters. RESULTS: The prevalence of CD4 þ CD25 þ T cells was significantly higher in the TILs than PBLs. The expression of CD4 þ CD25 þ regulatory T cells in cancer milieu correlated with the tumor grade, stage, and myometrium invasion. The expression of FOXP3 and GITR in CD4 þ CD25 þ regulatory T cells was lower in PBLs than TILs. Most tumor-infiltrating CD8 þ T cells were CD28 À CD45RA À CD45RO þ CCR7 À , suggesting good terminal differentiation. Most of them had an activated role with CD69 þ CD103 þ CD152 þ . Functionally, both granzyme B and perforin were scarcely expressed in peripheral regulatory T cells but were highly expressed in peripheral regulatory T cells in the tumor microenvironment. In contrast, CD8 þ cytotoxic T cells derived from PBLs expressed both granzyme B and perforin, and at significantly higher levels than in TILs. Further functional assays demonstrated that Th1 cytokines and cytotoxic molecules can be synchronously up-regulated in CD8 þ cytotoxic T cells. CONCLUSIONS: Regulatory T cells in the tumor microenvironment may abrogate CD8 þ T cell cytotoxicity in a granzyme B-and perforin-dependent conduit. Decreases in both Th1 cytokines and cytotoxic enzymes are relevant for regulatory T cell-mediated restraint of tumor clearance in vivo. Of clinical significance, the expression of regulatory T cells in TILs may mediate T cell immune repression within cancer milieu and thus greatly correlate with cancer progression. Cancer 2010;116:5777-88.

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Section: Regulatory T Cells In Endometrial Cancer/chang Et Almentioning

confidence: 99%

Section: Regulatory T Cells In Endometrial Cancer/chang Et Almentioning

confidence: 99%

Clinical significance of regulatory T cells and CD8+ effector populations in patients with human endometrial carcinoma

Chang

Huang

et al. 2010

Cancer

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“…TLRs are in serving as detectors of infectious diseases and cancer by activating dendritic cells (DCs) and other antigen-presenting cells to secrete proinflammatory cytokines and promoting DCs maturation to induct adaptive immune responses (Wang et al, 2008;Kumar et al, 2009). Ionizing radiation triggers production of generic "danger" signals may also activate effectors of innate immunity through TLR dependent mechanisms, and evoke the immune response to cancer (McBride et al, 2004;Roses et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

Lack of Association of Three Common Polymorphisms in Toll-like receptors (TLRs), TLR2+597T>C, +1350C>T and Arg753Gln with Cancer Risk: a Meta-analysis

Yang

Wang²,

Qiu³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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“…Given their critical role in regulating innate and acquired immunity, and as biomarkers of infectious pathogens and cancer debris, toll-like receptors (TLRs) were described as key players in the pathogenesis and progression of NPC (8,9). Dysregulation of TLR signaling imparts a higher risk of the development of chronic inflammatory diseases and cancers (10), in which TLR gene polymorphisms contribute to this dysregulation and thus to disease susceptibility and progression, including cancers.…”

Section: Introductionmentioning

confidence: 99%

TLR2 (-196 to -174 Ins/Del) and TLR3 (1377C>T) as biomarkers for nasopharyngeal cancer in Tunisia

Makni¹,

Messadi²,

Zidi³

et al. 2017

Turk J Med Sci

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Background/aim: We evaluated the association of TLR2 (-196 to -174 Ins/Del) and TLR3 (1377 C>T) as potential risk factors for nasopharyngeal carcinoma (NPC) in Tunisians. Material and methods:The study subjects comprised 137 NPC patients and 164 cancer-free control subjects. TLR2 genotyping was done by PCR and TLR3 genotyping was performed by PCR-RFLP.Results: Minor allele frequency (MAF) and genotypes of TLR3 (1377 C>T) were comparable between NPC patients and controls. Significantly higher MAF and TLR2-containing Del allele genotypes of TLR2 (-196 to -174 Ins/Del) were seen in NPC patients compared to controls [OR (95% CI) = 2.10 (1.43-3.08), P < 0.001 and OR (95% CI) = 2.07 (1.27-3.37), P = 0.003]. In addition, higher increased NPC risk was associated with the TLR2-Del/Del genotype [OR (95% CI) = 2.74 (1.37-5.48), P = 0.004]. An increased frequency of the Del-T haplotype was seen in NPC cases compared to controls. Conclusion:Our results demonstrate an increased risk of NPC with the TLR2-Del/Del genotype and Del-T TLR2 and TLR3 haplotype, suggesting their potential use as biomarkers to evaluate NPC risk in Tunisians.

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Toll-like receptors and immune regulation: implications for cancer therapy

Cited by 133 publications

References 109 publications

Clinical significance of regulatory T cells and CD8+ effector populations in patients with human endometrial carcinoma

Clinical significance of regulatory T cells and CD8+ effector populations in patients with human endometrial carcinoma

Lack of Association of Three Common Polymorphisms in Toll-like receptors (TLRs), TLR2+597T>C, +1350C>T and Arg753Gln with Cancer Risk: a Meta-analysis

TLR2 (-196 to -174 Ins/Del) and TLR3 (1377C>T) as biomarkers for nasopharyngeal cancer in Tunisia

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