The TNF Paradox in Cancer Progression and Immunotherapy

Montfort, Anne; Colacios, Céline; Levade, Thierry; Andrieu‐Abadie, Nathalie; Meyer, Nicolas; Ségui, Bruno

doi:10.3389/fimmu.2019.01818

Cited by 226 publications

(171 citation statements)

References 36 publications

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“…Recent evidences reported that HER2-overexpressing BC cells are susceptible to apoptosis induced in vitro by T helper 1 cytokines as TNF-α [46,47]. Through a complex regulatory network, after its receptor activation, TNF-α has been found to induce apoptosis or necrosis but also an opposite effect inducing cell growth, invasion or propagation of cancer cells [48,49]. Conversely, antigen-specific CD8+ T cells use TNF-α as part of their anti-tumor effector arsenal to better support the antibody-dependent cell-mediated cytotoxicity (ADCC) driven by trastuzumab.…”

Section: Discussionmentioning

confidence: 99%

Effect of Estrogen Receptor Status on Circulatory Immune and Metabolomics Profiles of HER2-Positive Breast Cancer Patients Enrolled for Neoadjuvant Targeted Chemotherapy

Vignoli

Muraro

Miolo

et al. 2020

Cancers

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HER2-positive breast cancer (BC) represents a heterogeneous cancer disease. In an attempt to identify new stratification models useful for prognosis and therapeutic strategy, we investigated the influence of estrogen receptor (ER) status on the host immune and metabolomics profile of HER2-positive BC patients enrolled for neoadjuvant targeted chemotherapy (NATC). The study enrolled 43 HER2-positive BC patients eligible for NATC based on the trastuzumab-paclitaxel combination. Baseline circulatory cytokines and 1H NMR plasma metabolomics profiles were investigated. Differences in the immune cytokines and metabolomics profile as a function of the ER status, and their association with clinical outcomes were studied by multivariate and univariate analysis. Baseline metabolomics profiles were found to discriminate HER2-positive ER(+) from ER(−) BC patients. Within the ER(+) group an immune-metabolomics model, based on TNF-α and valine, predicted pathological complete response to NATC with 90.9% accuracy (AUROC = 0.92, p = 0.004). Moreover, metabolomics information integrated with IL-2 and IL-10 cytokine levels were prognostic of relapse with an accuracy of 95.5%. The results indicate that in HER2-positive BC patients the ER status influences the host circulatory immune-metabolomics profile. The baseline immune-metabolomics assessment in combination with ER status could represent an independent stratification tool able to predict NATC response and disease relapse of HER2-positive patients.

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Section: Discussionmentioning

confidence: 99%

Effect of Estrogen Receptor Status on Circulatory Immune and Metabolomics Profiles of HER2-Positive Breast Cancer Patients Enrolled for Neoadjuvant Targeted Chemotherapy

Vignoli

Muraro

Miolo

et al. 2020

Cancers

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“…Both TNF- α and IL6 are known to have complex effects and dual roles in cancer (Bertazza and Mocellin, 2010 ; Fisher et al, 2014 ). Some studies have shown TNF-α to possess anti-tumor properties and can be exploited for treatment of some cancer types, while others have demonstrated it contributes to tumor progression by modulation of the immune response (Montfort et al, 2019 ). The overall effect seems to be dependent on its level, with high concentrations favoring tumor regression.…”

Section: Discussionmentioning

confidence: 99%

“…Similarly, increased expression of IL6 has been associated with tumor progression and metastasis but, at the same time, it is shown to augment adaptive immunity against tumor growth (Fisher et al, 2014 ). It has been emphasized that the biological outcome of these cytokines depends on multiple factors including cell type, concentration, tissue condition, tumor microenvironment, and cross talk between several signaling pathways activated at a particular time (Fisher et al, 2014 ; Montfort et al, 2019 ). We believe that further studies focusing on global transcriptome profiling are needed to get better understanding of biological mechanisms activated by commensals in OSCC cell lines.…”

Section: Discussionmentioning

confidence: 99%

Screening of Health-Associated Oral Bacteria for Anticancer Properties in vitro

Baraniya

Jain

Lucarelli

et al. 2020

Front. Cell. Infect. Microbiol.

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While extensive literature exists about the role of oral bacterial pathogens like Porphyromonas gingivalis and Fusobacterium nucleatum in oral squamous cell carcinoma (OSCC), the role of health-associated species has been largely unexplored. In this study, we assessed the effect of Streptococcus mitis, Rothia mucilaginosa, Neisseria flavescens, Haemophilus parainfluenzae, Lautropia mirabilis , and Veillonella parvula on proliferation and expression of marker genes (IL-6, TNF-α, MMP3, CD36, CCD1, and NANOG) in OSCC cell lines CAL27, SCC25, and SCC4. Porphyromonas gingivalis was included as a pathogenic control. Both bacterial lysates (3 concentrations) and live cells (3 MOIs) were tested. S. mitis, H. parainfluenzae , and N. flavescens resulted in substantial, dose-dependent reduction of proliferation, which was found to be mediated by H 2 O 2 for the former and intracellular infection in the latter two species. However, only H. parainfluenzae showed differential antiproliferative effect against the cancer cell lines vs. the normal control (TIGKs). In the gene expression assays, the health-associated species mostly downregulated CD36, a gene that plays an important role in tumor growth and metastasis, while P. gingivalis upregulated it. IL6 and TNF expression, on the other hand, was upregulated by almost all species, particularly the Gram-negatives including P. gingivalis . The effect on other genes was less evident and varied significantly by cell line. This exploratory study is the first insight into how health-associated bacteria may interact with OSCC. Further studies to explore whether the observed effects may have implications for the prevention or treatment of oral cancer are warranted.

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“…Mast cells produce Th2 cytokines which contributes to M2 (pro-tumor) polarization of tumor-associated macrophages, and the cells produce TNF-α and IL-10 which promote the Treg-mediated immune tolerance and immune tolerance against tumors [4][5][6]. Mast cells produce TGF-β, CXCL8, and TNF-α, promoting epithelial-to-mesenchymal transition in tumor invasion and metastasis [94][95][96]. Mast-cell-produced histamine was shown to inhibit hypoxia inducible factor-1 alpha expression and the followed growth suppression in melanoma [97].…”

Section: Involvement Of Kir2dl4 On Human Mast Cells In Tumor Progressionmentioning

confidence: 99%

Killer Immunoglobulin-Like Receptor 2DL4 (CD158d) Regulates Human Mast Cells both Positively and Negatively: Possible Roles in Pregnancy and Cancer Metastasis

Kataoka

Ueshima

Hirata

et al. 2020

IJMS

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Killer immunoglobulin-like receptor (KIR) 2DL4 (CD158d) was previously thought to be a human NK cell-specific protein. Mast cells are involved in allergic reactions via their KIT-mediated and FcɛRI-mediated responses. We recently detected the expression of KIR2DL4 in human cultured mast cells established from peripheral blood of healthy volunteers (PB-mast), in the human mast cell line LAD2, and in human tissue mast cells. Agonistic antibodies against KIR2DL4 negatively regulate the KIT-mediated and FcɛRI-mediated responses of PB-mast and LAD2 cells. In addition, agonistic antibodies and human leukocyte antigen (HLA)-G, a natural ligand for KIR2DL4, induce the secretion of leukemia inhibitory factor and serine proteases from human mast cells, which have been implicated in pregnancy establishment and cancer metastasis. Therefore, KIR2DL4 stimulation with agonistic antibodies and recombinant HLA-G protein may enhance both processes, in addition to suppressing mast-cell-mediated allergic reactions.

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The TNF Paradox in Cancer Progression and Immunotherapy

Cited by 226 publications

References 36 publications

Effect of Estrogen Receptor Status on Circulatory Immune and Metabolomics Profiles of HER2-Positive Breast Cancer Patients Enrolled for Neoadjuvant Targeted Chemotherapy

Effect of Estrogen Receptor Status on Circulatory Immune and Metabolomics Profiles of HER2-Positive Breast Cancer Patients Enrolled for Neoadjuvant Targeted Chemotherapy

Screening of Health-Associated Oral Bacteria for Anticancer Properties in vitro

Killer Immunoglobulin-Like Receptor 2DL4 (CD158d) Regulates Human Mast Cells both Positively and Negatively: Possible Roles in Pregnancy and Cancer Metastasis

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