The multifaceted role of TRAIL signaling in cancer and immunity

Alves, Ludmila Cardoso; Corazza, Nadia; Micheau, Olivier; Krebs, Philippe

doi:10.1111/febs.15637

Cited by 70 publications

(54 citation statements)

References 255 publications

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“…TNFRSF6B itself can attenuate inflammation and overexpression of this proteins has been related to breast cancer progression ( 37 , 38 ). TNFSF10 is another ligand with both pro- and anti-apoptotic effects as well as effects on the immune response ( 39 ). These data have been corroborated by genome wide screens that recently uncovered the TNF-pathway as essential for susceptibility of immunotherapy and important for the understanding of the immune response in cancer ( 40 ).…”

Section: Discussionmentioning

confidence: 99%

Breast Density and Estradiol Are Major Determinants for Soluble TNF-TNF-R Proteins in vivo in Human Breast Tissue

et al. 2022

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High mammographic density and exposure to sex steroids are independent risk factors for breast cancer by yet unknown mechanisms. Inflammation is one hallmark of cancer and the tumor necrosis factor family of proteins (TNFSFs) and receptors (TNFRSFs) are key determinants of tissue inflammation. The relationship between TNFSFs/TNFRSFs and breast tissue density or local breast estradiol levels is unknown. We investigated whether TNFSFs and soluble TNFRSFs (sTNFRSFs) are dysregulated in vivo in human breast cancer and dense breast tissue of postmenopausal women. We explored TNFSF/TNFRSF correlations with breast density and estradiol, both locally in the breast and in abdominal subcutaneous (s.c.) fat as a measure of systemic effects. Microdialysis was used for local sampling of in vivo proteins and estradiol in a total of 73 women; 12 with breast cancer, 42 healthy postmenopausal women with different breast densities, and 19 healthy premenopausal women. Breast density was determined as lean tissue fraction (LTF) using magnetic resonance imaging. Microdialysis was also performed in estrogen receptor (ER) positive breast cancer in mice treated with the pure anti-estrogen fulvestrant and tumor tissue was subjected to immunohistochemistry. 23 members of the TNFSF/sTNFRSF families were quantified using proximity extension assay.Our data revealed upregulation of TNFSF10, 13 and 13B, TNFRSF6, 6B, 9, 11A, 11B, 13B, 14, and 19, and TNFR-1 and -2 in ER+ breast cancer in women. In dense breast tissue TNFSF10, 13, and 14, TNFRSF3, 6, 9, 10B, 13B, 14, 19, and TNFR-1 and -2 were upregulated. Certain TNFSFs/TNFRSFs were increased in premenopausal breasts relative to postmenopausal breasts. Furthermore, estradiol correlated with most of the TNFSF/sTNFRSF members, though LTF only correlated with some of the proteins. Several of these associations were breast tissue-specific, as very few correlated with estradiol in abdominal s.c. fat. Estrogen dependent regulations of TNFSF2 (TNF-α) and TNF-R2 were corroborated in ER+ breast cancer in mice. Taken together, our data indicate TNFSFs/sTNFRSFs may represent potential targetable pathways for treatment of breast cancer patients and in prevention of breast cancer development in women with dense breasts.

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Section: Discussionmentioning

confidence: 99%

Breast Density and Estradiol Are Major Determinants for Soluble TNF-TNF-R Proteins in vivo in Human Breast Tissue

et al. 2022

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“…TNF-related apoptosis induced ligand (TRAIL) is a homotrimeric protein that its main role is for modulating immune responses ( 88 ). Expression of TRAIL on T and NK cells is important for controlling tumor immune surveillance ( 89 ). TRAIL type 2 receptor (TRAIL-R2) (also called death receptor 5/DR5) is a membrane-bound death receptor ( 90 ) that is expressed mainly on endothelial cells (ECs) and immune cells ( 88 ).…”

Section: Factors Related To the Differentiated Cellular State In Tumor Immune Ecosystemmentioning

confidence: 99%

(Im)maturity in Tumor Ecosystem

Mortezaee

Majidpoor

2022

Front. Oncol.

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Tumors have special features that make them distinct from their normal counterparts. Immature cells in a tumor mass and their critical contributions to the tumorigenesis will open new windows toward cancer therapy. Incomplete cellular development brings versatile and unique functionality in the cellular tumor ecosystem, such as what is seen for highly potential embryonic cells. There is evidence that maturation of certain types of cells in this ecosystem can recover the sensitivity of the tumor. Therefore, understanding more about the mechanisms that contributed to this immaturity will render new therapeutic approaches in cancer therapy. Targeting such mechanisms can be exploited as a supplementary to the current immunotherapeutic treatment schedules, such as immune checkpoint inhibitor (ICI) therapy. The key focus of this review is to discuss the impact of (im)maturity in cellular tumor ecosystems on cancer progression, focusing mainly on immaturity in the immune cell compartment of the tumor, as well as on the stemness of tumor cells.

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“…Activation of proinflammatory pathways by TRAIL increases proliferation, migration, invasion and/or metastasis of cancer cells, primarily through nuclear factor-kappa B (NF-κB), PI3K, AKT and MAPK [ 10 , 11 , 12 ]. Recent studies have confirmed that NF-κB is often constitutively activated in human cancer cells [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

OSMI-1 Enhances TRAIL-Induced Apoptosis through ER Stress and NF-κB Signaling in Colon Cancer Cells

Lee

Choi

Kwon

2021

IJMS

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Levels of O-GlcNAc transferase (OGT) and hyper-O-GlcNAcylation expression levels are associated with cancer pathogenesis. This study aimed to find conditions that maximize the therapeutic effect of cancer and minimize tissue damage by combining an OGT inhibitor (OSMI-1) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). We found that OSMI-1 treatment in HCT116 human colon cancer cells has a potent synergistic effect on TRAIL-induced apoptosis signaling. Interestingly, OSMI-1 significantly increased TRAIL-mediated apoptosis by increasing the expression of the cell surface receptor DR5. ROS-induced endoplasmic reticulum (ER) stress by OSMI-1 not only upregulated CHOP-DR5 signaling but also activated Jun-N-terminal kinase (JNK), resulting in a decrease in Bcl2 and the release of cytochrome c from mitochondria. TRAIL induced the activation of NF-κB and played a role in resistance as an antiapoptotic factor. During this process, O-GlcNAcylation of IκB kinase (IKK) and IκBα degradation occurred, followed by translocation of p65 into the nucleus. However, combination treatment with OSMI-1 counteracted the effect of TRAIL-mediated NF-κB signaling, resulting in a more synergistic effect on apoptosis. Therefore, the combined treatment of OSMI-1 and TRAIL synergistically increased TRAIL-induced apoptosis through caspase-8 activation. Conclusively, OSMI-1 potentially sensitizes TRAIL-induced cell death in HCT116 cells through the blockade of NF-κB signaling and activation of apoptosis through ER stress response.

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The multifaceted role of TRAIL signaling in cancer and immunity

Cited by 70 publications

References 255 publications

Breast Density and Estradiol Are Major Determinants for Soluble TNF-TNF-R Proteins in vivo in Human Breast Tissue

Breast Density and Estradiol Are Major Determinants for Soluble TNF-TNF-R Proteins in vivo in Human Breast Tissue

(Im)maturity in Tumor Ecosystem

OSMI-1 Enhances TRAIL-Induced Apoptosis through ER Stress and NF-κB Signaling in Colon Cancer Cells

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