• biologics
• melanoma
• psoriasis
• psoriatic arthritis
• skin cancer
• targeted therapies

• basal cell carcinoma
• check point inhibitors
• imiquimod
• immunotherapy

• Cytokine
• Interleukin-22
• Tumor

• Humans
• Interleukins/metabolism
• Interleukin-22
• Neoplasms/metabolism
• Neoplasms/immunology
• Neoplasms/pathology
• Animals
• Signal Transduction
• STAT3 Transcription Factor/metabolism
• Receptors, Interleukin/metabolism
• Receptors, Interleukin/genetics

• Th1 cells
• Th17 cells
• Th2 cells
• basal cell carcinoma
• squamous cell carcinoma
• tumor-infiltrating lymphocytes

• Humans
• Skin Neoplasms/immunology
• Skin Neoplasms/pathology
• Carcinoma, Squamous Cell/immunology
• Carcinoma, Squamous Cell/pathology
• Th17 Cells/immunology
• Lymphocytes, Tumor-Infiltrating/immunology
• Th1 Cells/immunology
• Carcinoma, Basal Cell/immunology
• Carcinoma, Basal Cell/pathology
• Female
• Male
• Aged
• Cross-Sectional Studies
• Middle Aged
• CD8-Positive T-Lymphocytes/immunology
• Aged, 80 and over
• Adult

• IMM/BI/82-2017 Almirall, S.A

• CD4 T lymphocytes
• T CD4 tumor response
• cancer
• tissue-specific immune response
• tumor immunology

• Animals
• Humans
• Adaptation, Physiological/immunology
• CD4-Positive T-Lymphocytes/immunology
• Cytokines/metabolism
• Cytokines/immunology
• Homeostasis/immunology
• Neoplasms/immunology
• Neoplasms/pathology
• Tumor Microenvironment/immunology

• Digital spatial profiler
• Immunosuppression
• PDT
• TGF-β blockade
• TGF-β1

• Humans
• Transforming Growth Factor beta1
• Photochemotherapy/methods
• Immunosuppression Therapy
• Neoplasms/drug therapy
• Transforming Growth Factor beta
• Cell Line, Tumor
• Tumor Microenvironment

• 82204340 National Natural Science Foundation of China
• 81801819 National Natural Science Foundation of China
• 82173954 National Natural Science Foundation of China
• BK20221048 Natural Science Foundation of Jiangsu Province of China
• 2022ZB295 Jiangsu Funding Program for Excellent Postdoctoral Talent
• 2022M723508 China Postdoctoral Science Foundation
• 2020M682230 China Postdoctoral Science Foundation
• 2021T140504 China Postdoctoral Science Foundation
• ZR2020MH295 Natural Science Foundation of Shandong Province of China
• 2022GSMPA-KL06 State Drug Administration-Key Laboratory of Quality Control of Chinese Medicinal Materials and Detection Pieces

• Basal cell
• Carcinoma
• Neoplasms
• Skin neoplasms
• Tumor-infiltrating lymphocytes

• anti-tumor immunity
• cancer
• clinical trials
• photodynamic therapy

• Humans
• Photochemotherapy/methods
• Adjuvants, Immunologic/therapeutic use
• Photosensitizing Agents/therapeutic use
• Neoplasms/drug therapy
• Neoplasms/pathology
• Immunotherapy/methods

• Plaque psoriasis
• anti-IL12/23
• anti-IL17
• anti-IL23
• anti-TNF
• biologics
• cost-effectiveness
• psoriasis vulgaris

• Humans
• Adalimumab/therapeutic use
• Ustekinumab/therapeutic use
• Infliximab/therapeutic use
• Treatment Outcome
• Psoriasis/drug therapy
• Biological Products/therapeutic use
• Severity of Illness Index

• Toll-like receptor 7
• adaptive immune system
• basal cell carcinoma
• checkpoint inhibitor
• epidemiology
• imiquimod
• immunosuppression
• immunotherapy
• innate immune system
• keratinocyte carcinoma
• pathogenesis
• programmed cell death 1
• risk factors
• solid organ transplant
• squamous cell carcinoma

• basal cell carcinoma
• immunotherapy
• squamous cell carcinoma
• tumor microenvironment

• R01 DE032018 NIDCR NIH HHS
• R01DE032018 NIH HHS
• R37 CA242006 NCI NIH HHS
• R37CA242006 NIH HHS
• P50 CA093459 NCI NIH HHS

Basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC), referred to as keratinocyte carcinomas, are skin cancer with the highest incidence. BCCs, rarely metastasize; whereas, though generally not characterized by high lethality, approximately 2–4% of primary cSCCs metastasize with patients exhibiting poor prognosis. The extracellular matrix (ECM) serves as a scaffold that provides structural and biological support to cells in all human tissues. The main components of the ECM, including fibrillar proteins, proteoglycans (PGs), glycosaminoglycans (GAGs), and adhesion proteins such as fibronectin, are secreted by the cells in a tissue-specific manner, critical for the proper function of each organ. The skin compartmentalization to the epidermis and dermis compartments is based on a basement membrane (BM), a highly specialized network of ECM proteins that separate and unify the two compartments. The stiffness and assembly of BM and tensile forces affect tumor progenitors' invasion at the stratified epithelium's stromal border. Likewise, the mechanical properties of the stroma, e.g., stiffness, are directly correlated to the pathogenesis of the keratinocyte carcinomas. Since the ECM is a pool for various growth factors, cytokines, and chemokines, its' intense remodeling in the aberrant cancer tissue milieu affects biological functions, such as angiogenesis, adhesion, proliferation, or cell motility by regulating specific signaling pathways. This review discusses the structural and functional modulations of the keratinocyte carcinoma microenvironment. Furthermore, we debate how ECM remodeling affects the pathogenesis of these skin cancers.

• basal cell carcinoma
• methotrexate

• central lung cancer
• chlorin е6
• fluorescent diagnosis
• indocyanine green
• lung cancer screening
• photodynamic theranostics
• photodynamic therapy
• photosensitizers

• Early Detection of Cancer
• Humans
• Lung Neoplasms/diagnosis
• Photochemotherapy/methods
• Photosensitizing Agents/therapeutic use
• Precision Medicine

• Cancer
• Immune response
• Interleukin-17
• Pathophysiology
• Th17 cells
• Tumor microenvironment

Reactive oxygen species (ROS) have been subject of increasing interest in the pathophysiology and therapy of cancers in recent years. In skin cancer, ROS are involved in UV-induced tumorigenesis and its targeted treatment via, e.g., photodynamic therapy. Another recent technology for topical ROS generation is cold physical plasma, a partially ionized gas expelling dozens of reactive species onto its treatment target. Gas plasma technology is accredited for its wound-healing abilities in Europe, and current clinical evidence suggests that it may have beneficial effects against actinic keratosis. Since the concept of hormesis dictates that low ROS levels perform signaling functions, while high ROS levels cause damage, we investigated herein the antitumor activity of gas plasma in non-melanoma skin cancer. In vitro, gas plasma exposure diminished the metabolic activity, preferentially in squamous cell carcinoma cell (SCC) lines compared to non-malignant HaCaT cells. In patient-derived basal cell carcinoma (BCC) and SCC samples treated with gas plasma ex vivo, increased apoptosis was found in both cancer types. Moreover, the immunomodulatory actions of gas plasma treatment were found affecting, e.g., the expression of CD86 and the number of regulatory T-cells. The supernatants of these ex vivo cultured tumors were quantitatively screened for cytokines, chemokines, and growth factors, identifying CCL5 and GM-CSF, molecules associated with skin cancer metastasis, to be markedly decreased. These findings suggest gas plasma treatment to be an interesting future technology for non-melanoma skin cancer topical therapy.

• ROS
• chemokines
• cold physical plasma
• cytokines
• reactive oxygen species
• skin cancer

• BCC
• MMP
• TIMP
• invasion
• tumor progression

• Carcinoma, Basal Cell/blood supply
• Carcinoma, Basal Cell/enzymology
• Carcinoma, Basal Cell/pathology
• Collagenases/metabolism
• Humans
• Neoplasm Invasiveness
• Neoplasm Proteins/metabolism
• Neovascularization, Pathologic/enzymology
• Neovascularization, Pathologic/pathology
• Skin Neoplasms/blood supply
• Skin Neoplasms/enzymology
• Skin Neoplasms/pathology
• Tumor Microenvironment/radiation effects
• Ultraviolet Rays/adverse effects

Basal cell carcinoma (BCC) is the most common skin cancer and human malignancy. By analyzing BCC RNA sequencing data according to clinically important features, we identified novel differentially regulated genes and new targetable pathways. Several biomarkers were validated in patient-derived BCC samples.

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.

Photodynamic therapy (PDT) causes selective damage to tumor cells and vasculature and also triggers an anti-tumor immune response. The latter fact has prompted the exploration of PDT as an immune-stimulatory adjuvant. PDT is not the only cancer treatment that relies on electromagnetic energy to destroy cancer tissue. Ionizing radiation therapy (RT) and photothermal therapy (PTT) are two other treatment modalities that employ photons (with wavelengths either shorter or longer than PDT, respectively) and also cause tissue damage and immunomodulation. Research on the three modalities has occurred in different “silos”, with minimal interaction between the three topics. This is happening at a time when immune checkpoint inhibition (ICI), another focus of intense research and clinical development, has opened exciting possibilities for combining PDT, PTT, or RT with ICI to achieve improved therapeutic benefits. In this review, we surveyed the literature for studies that describe changes in anti-tumor immunity following the administration of PDT, PTT, and RT, including efforts to combine each modality with ICI. This information, collected all in one place, may make it easier to recognize similarities and differences and help to identify new mechanistic hypotheses toward the goal of achieving optimized combinations and tumor cures.

• clinical trials
• immune checkpoint inhibition
• immunotherapy
• murine models
• photodynamic therapy
• photothermal therapy
• radiation therapy

Basal cell carcinoma (BCC) is the most common malignant skin tumor. BCC displays a different behavior compared with other neoplasms, has a slow evolution, and metastasizes very rarely, but sometimes it causes an important local destruction. Chronic ultraviolet exposure along with genetic factors are the most important risk factors involved in BCC development. Mutations in the PTCH1 gene are associated with Gorlin syndrome, an autosomal dominant disorder characterized by the occurrence of multiple BCCs, but are also the most frequent mutations observed in sporadic BCCs. PTCH1 encodes for PTCH1 protein, the most important negative regulator of the Hedgehog (Hh) pathway. There are numerous studies confirming Hh pathway involvement in BCC pathogenesis. Although Hh pathway has been intensively investigated, it remains incompletely elucidated. Recent studies on BCC tumorigenesis have shown that in addition to Hh pathway, there are other signaling pathways involved in BCC development. In this review, we present recent advances in BCC carcinogenesis.

• Hedgehog pathway
• basal cell carcinoma
• carcinogenesis
• signaling pathways

• Animals
• Autoimmunity
• Carcinogenesis/immunology
• Disease Models, Animal
• Humans
• Inflammation/immunology
• Interleukin-17/metabolism
• Mice
• Review Literature as Topic
• Skin/immunology
• Skin/pathology
• Skin Diseases/immunology
• Skin Diseases/pathology
• Th17 Cells/immunology
• Th17 Cells/metabolism
• Tumor Microenvironment/immunology

• Basal cell carcinoma
• Cutaneous melanoma
• Reflectance confocal microscopy
• Skin cancer
• Squamous cell carcinoma
• Tumour microenvironment

Photodynamic therapy (PDT) is an anticancer strategy utilizing light-mediated activation of a photosensitizer (PS) which has accumulated in tumor and/or surrounding vasculature. Upon activation, the PS mediates tumor destruction through the generation of reactive oxygen species and tumor-associated vasculature damage, generally resulting in high tumor cure rates. In addition, a PDT-induced immune response against the tumor has been documented in several studies. However, some contradictory results have been reported as well. With the aim of improving the understanding and awareness of the immunological events triggered by PDT, this review focuses on the immunological effects post-PDT, described in preclinical and clinical studies. The reviewed preclinical evidence indicates that PDT is able to elicit a local inflammatory response in the treated site, which can develop into systemic antitumor immunity, providing long-term tumor growth control. Nevertheless, this aspect of PDT has barely been explored in clinical studies. It is clear that further understanding of these events can impact the design of more potent PDT treatments. Based on the available preclinical knowledge, recommendations are given to guide future clinical research to gain valuable information on the immune response induced by PDT. Such insights directly obtained from cancer patients can only improve the success of PDT treatment, either alone or in combination with immunomodulatory approaches.

• immunogenic cell death
• immunomodulation
• innate and adaptive immunity
• photodynamic therapy

The management of thromboangiitis obliterans (TAO) remains a medical challenge because of its unknown etiology. It is also not known whether it is a systemic or localized disease or a type of autoimmune vasculitis.

In this study, we evaluated the serum level of IL-17 and IL-23 which increase in both systemic inflammation and autoimmunity, in 60 TAO patients and 30 age- and smoking habit-matched controls. Also, IL-22, which has reported high level during infection but not in autoimmunity, was evaluated.

The serum levels of IL-17, IL-22 and IL-23 were significantly higher in the TAO patients in comparison with the controls (P<0.001). Notably, the serum levels of IL-17, IL-22 and IL-23 were highest in the patients with the chief complaint of chronic ulcer and lowest in the patients with gangrene (P<0.05). Also, the serum level of IL-22 was significantly higher in the anemic patients in comparison with the non-anemic patients (P=0.03).

Owing to our findings, TAO appears more likely to be a systemic disorder rather than a localized vasculopathy. Therefore, treatment protocols based on systemic treatment of TAO patients may be more helpful than localized treatment, such as bypass surgery and endovascular procedures. Also, according to our findings regarding the high level of IL-22, the trigger of TAO development may be an infectious pathogen. However, additional research is highly recommended to investigate whether TAO is an infectious disease or an infectious-induced autoimmunity.

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• Buerger’s disease
• autoimmunity
• interleukin-17
• interleukin-22
• interleukin-23
• thromboangiitis obliterans

• TERT promoter
• cutaneous squamous cell carcinoma
• telomerase
• telomere

• Bowen's Disease/genetics
• Bowen's Disease/pathology
• Carcinoma, Squamous Cell/genetics
• Carcinoma, Squamous Cell/pathology
• Disease Progression
• Germ Cells/pathology
• Humans
• Keratosis, Actinic/genetics
• Keratosis, Actinic/pathology
• Mutation
• Skin Neoplasms/genetics
• Skin Neoplasms/pathology
• Telomerase/genetics
• Telomere/genetics
• Telomere Shortening/genetics

• Breg
• Th17
• Treg
• primary hepatic carcinoma (PHC)
• tumour microenvironment

(1) Background: Non-melanoma skin cancer is the most frequently diagnosed cancer in humans. The process of skin carcinogenesis is still not fully understood. However, several studies have been conducted to better explain the mechanisms that lead to malignancy; (2) Methods: We reviewed the more recent literature about the pathogenesis of non-melanoma skin cancer focusing on basal cell carcinomas, squamous cell carcinoma and actinic keratosis; (3) Results: Several papers reported genetic and molecular alterations leading to non-melanoma skin cancer. Plenty of risk factors are involved in non-melanoma skin cancer pathogenesis, including genetic and molecular alterations, immunosuppression, and ultraviolet radiation; (4) Conclusion: Although skin carcinogenesis is still not fully understood, several papers demonstrated that genetic and molecular alterations are involved in this process. In addition, plenty of non-melanoma skin cancer risk factors are now known, allowing for an effective prevention of non-melanoma skin cancer development. Compared to other papers on the same topic, our review focused on molecular and genetic factors and analyzed in detail several factors involved in non-melanoma skin cancer.

• actinic keratosis
• pathogenesis
• precancerous conditions
• skin neoplasms

Basal cell carcinoma (BCC) is the most common human cancer and represents a growing public health care problem. Several tumor suppressor genes and proto-oncogenes have been implicated in BCC pathogenesis, including the key components of the Hedgehog pathway, PTCH1 and SMO, the TP53 tumor suppressor, and members of the RAS proto-oncogene family. Aberrant activation of the Hedgehog pathway represents the molecular driver in basal cell carcinoma pathogenesis, with the majority of BCCs carrying somatic point mutations, mainly ultraviolet (UV)-induced, and/or copy-loss of heterozygosis in the PTCH1 gene. Recent advances in sequencing technology allowed genome-scale approaches to mutation discovery, identifying new genes and pathways potentially involved in BCC carcinogenesis. Mutational and functional analysis suggested PTPN14 and LATS1, both effectors of the Hippo–YAP pathway, and MYCN as new BCC-associated genes. In addition, emerging reports identified frequent non-coding mutations within the regulatory promoter sequences of the TERT and DPH3-OXNAD1 genes. Thus, it is clear that a more complex genetic network of cancer-associated genes than previously hypothesized is involved in BCC carcinogenesis, with a potential impact on the development of new molecular targeted therapies. This article reviews established knowledge and new hypotheses regarding the molecular genetics of BCC pathogenesis.

• DPH3 promoter
• LATS1
• MYCN
• PTCH1
• PTPN14
• TERT promoter
• TP53
• basal cell carcinoma
• molecular genetics

• Animals
• Biomarkers
• Carcinoma, Basal Cell/genetics
• Carcinoma, Basal Cell/metabolism
• Carcinoma, Basal Cell/pathology
• Carcinoma, Basal Cell/therapy
• Cell Transformation, Neoplastic/genetics
• Gene Expression Regulation, Neoplastic
• Genetic Predisposition to Disease
• Genetic Therapy
• Humans
• Loss of Heterozygosity
• Mutation
• Proto-Oncogene Mas
• Signal Transduction
• Skin Neoplasms/genetics
• Skin Neoplasms/metabolism
• Skin Neoplasms/pathology
• Skin Neoplasms/therapy