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      Cutaneous Squamous Cell Carcinoma Arising in Immunosuppressed Patients: A Systematic Review of Tumor Profiling Studies

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          Abstract

          As solid organ transplantation becomes more prevalent, more individuals are living as members of the immunosuppressed population with an elevated risk for cutaneous squamous cell carcinoma (cSCC). Although great progress has been made in understanding the pathogenesis of cSCC in general, little is known about the drivers of tumorigenesis in immunosuppressed patients and organ-transplant recipients, specifically. This systematic review sought to synthesize information regarding the genetic and epigenetic alterations as well as changes in protein and mRNA expression that place this growing population at risk for cSCC, influence treatment response, and promote tumor aggressiveness. This review will provide investigators with a framework to identify future areas of investigation and clinicians with additional insight into how to best manage these patients.

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          Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement.

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            S100 proteins in cancer.

            In humans, the S100 protein family is composed of 21 members that exhibit a high degree of structural similarity, but are not functionally interchangeable. This family of proteins modulates cellular responses by functioning both as intracellular Ca(2+) sensors and as extracellular factors. Dysregulated expression of multiple members of the S100 family is a common feature of human cancers, with each type of cancer showing a unique S100 protein profile or signature. Emerging in vivo evidence indicates that the biology of most S100 proteins is complex and multifactorial, and that these proteins actively contribute to tumorigenic processes such as cell proliferation, metastasis, angiogenesis and immune evasion. Drug discovery efforts have identified leads for inhibiting several S100 family members, and two of the identified inhibitors have progressed to clinical trials in patients with cancer. This Review highlights new findings regarding the role of S100 family members in cancer diagnosis and treatment, the contribution of S100 signalling to tumour biology, and the discovery and development of S100 inhibitors for treating cancer.
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              Multimodal Analysis of Composition and Spatial Architecture in Human Squamous Cell Carcinoma

              Summary To define the cellular composition and architecture of cutaneous squamous cell carcinoma (cSCC), we combined single-cell RNA sequencing with spatial transcriptomics and multiplexed ion beam imaging from a series of human cSCCs and matched normal skin. cSCC exhibited four tumor subpopulations, three recapitulating normal epidermal states, and a tumor-specific keratinocyte (TSK) population unique to cancer, which localized to a fibrovascular niche. Integration of single-cell and spatial data mapped ligand-receptor networks to specific cell types, revealing TSK cells as a hub for intercellular communication. Multiple features of potential immunosuppression were observed, including T regulatory cell (Treg) co-localization with CD8 T cells in compartmentalized tumor stroma. Finally, single-cell characterization of human tumor xenografts and in vivo CRISPR screens identified essential roles for specific tumor subpopulation-enriched gene networks in tumorigenesis. These data define cSCC tumor and stromal cell subpopulations, the spatial niches where they interact, and the communicating gene networks that they engage in cancer.
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                Author and article information

                Contributors
                Journal
                JID Innov
                JID Innov
                JID Innovations
                Elsevier
                2667-0267
                30 March 2022
                July 2022
                30 March 2022
                : 2
                : 4
                : 100126
                Affiliations
                [1 ]Department of Dermatology, University of Nebraska Medical Center, Omaha, Nebraska, USA
                [2 ]Department of Dermatology, Oregon Health & Science University, Portland, Oregon, USA
                [3 ]College of Medicine, University of Nebraska Medical Center, Omaha, Nebraska, USA
                [4 ]Library Services, Creighton University, Omaha, Nebraska
                Author notes
                []Correspondence: Melodi Javid Whitley, MD, PhD, Department of Dermatology, College of Medicine, University of Nebraska Medical Center, 4014 Leavenworth Street, Omaha, Nebraska 68198-5645, USA. mwhitley@ 123456unmc.edu
                [5]

                These authors contributed equally to this work.

                Article
                S2667-0267(22)00034-0 100126
                10.1016/j.xjidi.2022.100126
                9127418
                ebd59d60-c106-4165-bd2a-dd1bf31c1898
                © 2022 The Authors. Published by Elsevier, Inc. on behalf of the Society for Investigative Dermatology.

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 5 October 2021
                : 8 February 2022
                : 4 March 2022
                Categories
                Review

                6-tg, 6-thioguanine,aza, azathioprine,cni, calcineurin inhibitor,csa, cyclosporine,cscc, cutaneous squamous cell carcinoma,hbd, human β-defensin,icp, immunocompetent patient,isp, immunosuppressed patient,mirna, microrna,nmsc, nonmelanoma skin cancer,otr, organ-transplant recipient,p-smad, phosphorylated smad,rtr, renal transplant recipient,scc, squamous cell carcinoma,stat, signal transducer and activator of transcription,tak1, tgfβ-activated kinase 1,vno, voriconazole-n-oxide

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