In silico analyses of the tumor microenvironment highlight tumoral inflammation, a Th2 cytokine shift and a mesenchymal stem cell-like phenotype in advanced in basal cell carcinomas

Lefrançois, Pascale; Xie, Pingxing; Gunn, Scott R.; Gantchev, Jennifer; Villarreal, Amelia Martínez; Sasseville, Denis; Litvinov, Ivan V.

doi:10.1007/s12079-020-00563-6

Cited by 20 publications

(22 citation statements)

References 42 publications

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“…Th1-mediated interferon-g (IFn-g) is proved to be necessary for facilitating macrophages to kill cancer cells and up-regulating MHC molecules on cancer cells leading to enhance T cell recognition (83,84). On the other hand, the Th2-type cytokine pattern is more preferential in the malignant tumor and participated in cancer progression and immune evasion (85)(86)(87). In addition, Chae's work also revealed that platelets are the source of circulating DKK1 (66).…”

Section: Immunoregulatory Effects Of Dkk1mentioning

confidence: 99%

Dickkopf-1: A Promising Target for Cancer Immunotherapy

et al. 2021

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Clinical studies in a range of cancers have detected elevated levels of the Wnt antagonist Dickkopf-1 (DKK1) in the serum or tumors of patients, and this was frequently associated with a poor prognosis. Our analysis of DKK1 gene profile using data from TCGA also proves the high expression of DKK1 in 14 types of cancers. Numerous preclinical studies have demonstrated the cancer-promoting effects of DKK1 in both in vitro cell models and in vivo animal models. Furthermore, DKK1 showed the ability to modulate immune cell activities as well as the immunosuppressive cancer microenvironment. Expression level of DKK1 is positively correlated with infiltrating levels of myeloid-derived suppressor cells (MDSCs) in 20 types of cancers, while negatively associated with CD8+ T cells in 4 of these 20 cancer types. Emerging experimental evidence indicates that DKK1 has been involved in T cell differentiation and induction of cancer evasion of immune surveillance by accumulating MDSCs. Consequently, DKK1 has become a promising target for cancer immunotherapy, and the mechanisms of DKK1 affecting cancers and immune cells have received great attention. This review introduces the rapidly growing body of literature revealing the cancer-promoting and immune regulatory activities of DKK1. In addition, this review also predicts that by understanding the interaction between different domains of DKK1 through computational modeling and functional studies, the underlying functional mechanism of DKK1 could be further elucidated, thus facilitating the development of anti-DKK1 drugs with more promising efficacy in cancer immunotherapy.

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Section: Immunoregulatory Effects Of Dkk1mentioning

confidence: 99%

Dickkopf-1: A Promising Target for Cancer Immunotherapy

et al. 2021

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“…Primary RNA-Seq analysis was performed as previously reported ( 44 ). Raw fastq files were curated to remove low-quality reads using FastX-Toolkit.…”

Section: Methodsmentioning

confidence: 99%

The transcriptional landscape analysis of basal cell carcinomas reveals novel signalling pathways and actionable targets

et al. 2021

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Basal cell carcinoma (BCC) is the most common skin cancer and human malignancy. Although most BCCs are easily managed, some are aggressive locally, require Mohs micrographic surgery, or can even metastasize. In the latter, resistance to Sonic Hedgehog inhibitors may occur. Despite their frequent occurrence in clinical practice, their transcriptional landscape remains poorly understood. By analyzing BCC RNA sequencing data according to clinically important features (all BCCs versus normal skin, high-risk versus low-risk BCCs based solely on histopathological subtypes with aggressive features, advanced versus non-advanced BCCs, and vismodegib-resistant versus vismodegib-sensitive tumors), we have identified novel differentially regulated genes and new targetable pathways implicated in BCC tumorigenesis. Pathways as diverse as IL-17, TLR, Akt/PI3K, cadherins, integrins, PDGF, and Wnt/β-catenin are promising therapeutic avenues for local and systemic agents in managing this common malignancy, including through drug re-purposing of existing medications. We experimentally validated several of these targets as biomarkers in our patient-derived cohort of primary BCC tumors.

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“…The expression of CD103 in epithelial skin tumors has hardly been studied. This is surprising since (i) basal cell carcinomas (BCC) [ 91 , 92 , 93 ] and cutaneous squamous cell carcinomas (cSCC) [ 94 , 95 , 96 ] are by far the most common tumors of (especially fair-skinned) humans, (ii) these tumors are usually immunogenic [ 97 , 98 , 99 ], (iii) they often respond to topical and/or systemic immune modulation [ 100 , 101 , 102 , 103 , 104 ], and (iv) their incidence increases greatly upon immunosuppression [ 105 , 106 ]. Moreover, it was already described more than a quarter of a century ago that malignant T cells of cutaneous T cell lymphomas with high CD103 expression migrate preferentially into the E-cadherin-bearing epidermis [ 107 , 108 ].…”

Section: Cd103 In Epithelial Skin Tumorsmentioning

confidence: 99%

Integrin αE(CD103)β7 in Epithelial Cancer

Hoffmann

Schön

2021

Cancers

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Interactions of both the innate and the adaptive immune system with tumors are complex and often influence courses and therapeutic treatments in unanticipated ways. Based on the concept that CD8+T cells can mediate important antitumor effects, several therapies now aim to amplify their specific activity. A subpopulation of CD8+ tissue-resident T lymphocytes that express the αE(CD103)β7 integrin has raised particular interest. This receptor presumably contributes to the recruitment and retention of tumor-infiltrating immune cells through interaction with its ligand, E-cadherin. It appears to have regulatory functions and is thought to be a component of some immunological synapses. In TGF-rich environments, the αE(CD103)β7/E-cadherin-interaction enhances the binding strength between tumor cells and infiltrating T lymphocytes. This activity facilitates the release of lytic granule contents and cytokines as well as further immune responses and the killing of target cells. Expression of αE(CD103)β7 in some tumors is associated with a rather favorable prognosis, perhaps with the notable exception of squamous cell carcinoma of the skin. Although epithelial skin tumors are by far the most common tumors of fair-skinned people, there have been very few studies on the distribution of αE(CD103)β7 expressing cells in these neoplasms. Given this background, we describe here that αE(CD103)β7 is scarcely present in basal cell carcinomas, but much more abundant in squamous cell carcinomas with heterogeneous distribution. Notwithstanding a substantial number of studies, the role of αE(CD103)β7 in the tumor context is still far from clear. Here, we summarize the essential current knowledge on αE(CD103)β7 and outline that it is worthwhile to further explore this intriguing receptor with regard to the pathophysiology, therapy, and prognosis of solid tumors.

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In silico analyses of the tumor microenvironment highlight tumoral inflammation, a Th2 cytokine shift and a mesenchymal stem cell-like phenotype in advanced in basal cell carcinomas

Cited by 20 publications

References 42 publications

Dickkopf-1: A Promising Target for Cancer Immunotherapy

Dickkopf-1: A Promising Target for Cancer Immunotherapy

The transcriptional landscape analysis of basal cell carcinomas reveals novel signalling pathways and actionable targets

Integrin αE(CD103)β7 in Epithelial Cancer

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