The novel coronavirus SARS-CoV-2 enters into the human body mainly through the ACE2 + TMPRSS2+ nasal epithelial cells. The initial host response to this pathogen occurs in a peculiar immune ...microenvironment that, starting from the Nasopharynx-Associated Lymphoid Tissue (NALT) system, is the product of a long evolutionary process that is aimed to first recognize exogenous airborne agents. In the present work, we want to critically review the latest molecular and cellular findings on the mucosal response to SARS-CoV-2 in the nasal cavity and in NALT, and to analyze its impact in the subsequent course of COVID-19. Finally, we want to explore the possibility that the regulation of the systemic inflammatory network against the virus can be modulated starting from the initial phases of the nasal and nasopharyngeal response and this may have several clinical and epidemiological implications starting from a mucosal vaccine development.
Abstract Background Multi-step cancerogenesis guides laryngeal cancer onset and it includes a wide variety of pre-cancerous lesions macroscopically challenging to identify and distinguish from ...initial cancerous foci. Object Different modalities of diagnostic techniques of laryngeal epithelial lesions exist and they do not offer a single system to make a differential diagnosis. Hence, this meta-analysis aimed to synthesize the validity of each single diagnostic tool to improve laryngeal patient management. Methods A systematic review of literature was led searching for articles mentioning the following terms: larynx, laryngeal precancerous lesions, laryngeal cancer, white light (WL) endoscopy, stroboscopy, contact endoscopy (CE), autofluorescence (AF), ultrasound (US), narrow band imaging (NBI), computed axial tomography (CAT), magnetic resonance imaging (MRI), positron emission tomography (PET), CAT/PET. Then, a quantitative analysis was carried on for paper published after 2005 onward. Results The search identified 7215 publications, of which 3616 published after 2005, with a final results of a total of 214 articles stratified and included by our selection criteria. 42 out of 214 articles were selected for quantitative synthesis. 25 out of 41 studies had a good quality score, 16 were fair. Conclusions A comprehensive overview of the most recent advances in laryngeal imaging technology combined with all of the information needed to interpret findings and manage patients with voice disorders can be found herein. Our flow-chart allows clinicians in risk-stratify patients and select proper examination modalities to provide appropriate care. Study limitations, together with possible clinical and research implications have been counted.
Summary There is increasing evidence that the growth and spread of cancer is driven by a small subpopulation of cancer cells, defined as cancer stem cells (CSCs). Recent data indicate that the ...initiation, growth, recurrence and metastasis of cancers are related to the behavior of a small population of malignant cells with properties of stem cells, and information about them are potentially helpful in identifying the target for the tumor’s therapeutic elimination. The presence of subpopulation cells with phenotypic and behavioral characteristics corresponding to both normal epithelial stem cells and to cells capable of initiating tumors has been also reported in head and neck squamous cell carcinomas (HNSCCs).
Background Protection against helminths consists of adaptive responses by TH 2 cells and innate responses by group 2 innate lymphoid cells (ILC2s), with these latter being well characterized in mice ...but less so in human subjects. Objective We sought to characterize human circulating ILC2s and compare their functional profile with that of autologous TH 2 cells. Methods Circulating ILC2s and TH 2 cells were isolated by means of fluorescence-activated cell sorting and magnetic cell sorting and expanded in vitro . ILC2s were then stimulated with phorbol 12-myristate 13-acetate plus ionomycin, IL-25 plus IL-33 (IL-25/IL-33), or a mixture of Toll-like receptor ligands to evaluate their ability to produce cytokines, express CD154, and induce IgE production by autologous B cells. Cytokines and transcription factor gene methylation were assessed. Results ILC2s expressed GATA-3, retinoic acid orphan receptor (RORC) 2, and RORα; were able to produce IL-5, IL-13, and IL-4; and, accordingly, were characterized by demethylation of IL4 , IL13 , IL5 , GATA3 , and RORC2 , whereas the IFNG , IFNG promoter, and TBX21 regions of interest were methylated. ILC2s expressed TLR1 , TLR4 , and TLR6 , and TLR stimulation induced IL-5 and IL-13 production. Moreover, ILC2s expressed CD154 in response to phorbol 12-myristate 13-acetate plus ionomycin, IL-25/IL-33, or a mixture of TLR ligands. Stimulated ILC2s also induced IgM, IgG, IgA, and IgE production by B cells. Finally, circulating ILC2s from atopic patients were not different in numbers and frequency but expressed higher IL-4 levels than those from nonatopic subjects. Conclusion This study provides the first evidence that human ILC2s can express CD154 and stimulate the production of IgE by B lymphocytes through IL-25/IL-33 stimulation or TLR triggering.
Recurrent laryngeal carcinoma presents differences from the primary tumor that largely depend on the treatment. In this article, we review the histologic and molecular treatment-induced changes that ...may affect the diagnosis of recurrent laryngeal carcinoma, the assessment of predictive markers, and the response to treatment with immune checkpoint inhibitors. Radiotherapy induces profound modifications that are strictly related to necrosis of different tissue components, fibrosis, and damage of the tumor vessels. Postradiotherapy recurrent/persistent laryngeal squamous cell carcinoma typically presents a discohesive growth pattern within a fibrotic background associated with significant changes of the tumor immune microenvironment, with both important immunosuppressive and immunostimulatory effects. Overall, the increase of immunoregulatory cells and immune checkpoints such as CTLA-4, TIM-3, PD-1, and PD-L1 induced by radiotherapy and chemotherapy strongly supports the use of immune checkpoint inhibitors in recurrent/persistent laryngeal carcinoma. Future studies aiming to identify predictive factors of the response to immune checkpoint inhibitors should consider such treatment-induced modifications.
Head and neck (HN) cancer, which mainly presents in the form of squamous cell carcinoma, was the seventh most common cancer worldwide in 2018, with approximately 890,000 new cases and 450,000 deaths .......
The mismatch repair (MMR) system has a major role in the detection and correction of DNA replication errors, resulting from DNA polymerase slippage or nucleotides misincorporation. Specific ...inherited/acquired alterations or epigenetic inactivation of MMR genes are associated with microsatellite instability (MSI): the loss of crucial function in repairing DNA alterations can promote carcinogenesis by favoring the accumulation of thousands of mutations in a broad spectrum of different anatomic sites such as colon, stomach, prostate, esophagus, endometrium, lung and head and neck. Recent extensive data suggest that tumor mutational burden strongly correlates with a clinical response to immunotherapy using checkpoint inhibitors and this response is influenced by MMR deficiency in a wide range of human solid cancers. In this context, few data about this crucial point are available for head and neck cancer (HNC). In this review, we discuss the role of MMR alterations and the resulting MSI in HNC pathogenesis. Furthermore, by summarizing the clinical available data on how they influence the progression of precancerous lesions and the risk of recurrence or second primary tumors, we want to define the current role of MSI in the management of HNC. Finally, we analyze the complex interaction between cancer cells and the immune system addressing the data now available about a potential correlation between microsatellite instability and immunotherapy response in HNC.
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