Over the last decades, nitric oxide(NO) has been definitively recognised as one of the key players involved in immunity and inflammation. NO generation was originally described in activated macrophages, which still re...Over the last decades, nitric oxide(NO) has been definitively recognised as one of the key players involved in immunity and inflammation. NO generation was originally described in activated macrophages, which still represent the prototype of NO-producing cells. Notwithstanding, additional cell subsets belonging to both innate and adaptive immunity have been documented to sustain NO propagation by means of the enzymatic activity of different nitric oxide synthase isoforms. Furthermore, due to its chemical characteristics, NO could rapidly react with other free radicals to generate different reactive nitrogen species(RNS), which have been intriguingly associated with many pathological conditions. Nonetheless, the plethora of NO/RNS-mediated effects still remains extremely puzzling. The aim of this manuscript is to dig into the broad literature on the topic to provide intriguing insights on NO-mediated circuits within immune system. We analysed NO and RNS immunological clues arising from their biochemical properties, immunomodulatory activities and finally dealing with their impact on different pathological scenarios with far prompting intriguing perspectives for their pharmacological targeting.展开更多
Dear Editor,Anaplastic lymphoma kinase-positive(ALK+)anaplastic large cell lymphoma(ALCL)is an aggressive peripheral Tcell lymphoma representing 10%-15%of pediatric lymphoid neoplasms.The constitutively activated nucl...Dear Editor,Anaplastic lymphoma kinase-positive(ALK+)anaplastic large cell lymphoma(ALCL)is an aggressive peripheral Tcell lymphoma representing 10%-15%of pediatric lymphoid neoplasms.The constitutively activated nucleophosmin-ALK(NPM-ALK)fusion protein is the main driver of ALK+ALCL oncogenesis[1].Current clinical protocols can achieve high cure rates,with 75%event-free survival(EFS)at 5 years[2],but the patients’outcome with relapsed/refractory disease still remains poor[3].Liquid biopsy is widely applied for the prognostic and therapeutic stratification of onco-hematological patients.As a non-invasive procedure,it can be used to identify several biomarkers,such as small extracellular vesicles(S-EVs)[4].S-EVs are stable carriers of molecules that mediate genetic exchange between distant cells,alter the microenvironment,facilitate cancer cell progression and promote drug resistance[5].展开更多
基金Supported by Grant from the Italian Ministry of Health,BANDO GIOVANI RICERCATORI,No.2009-GR-2009-1558698Agnellini AHR was granted by Cariparo Fundation Fellowship
文摘Over the last decades, nitric oxide(NO) has been definitively recognised as one of the key players involved in immunity and inflammation. NO generation was originally described in activated macrophages, which still represent the prototype of NO-producing cells. Notwithstanding, additional cell subsets belonging to both innate and adaptive immunity have been documented to sustain NO propagation by means of the enzymatic activity of different nitric oxide synthase isoforms. Furthermore, due to its chemical characteristics, NO could rapidly react with other free radicals to generate different reactive nitrogen species(RNS), which have been intriguingly associated with many pathological conditions. Nonetheless, the plethora of NO/RNS-mediated effects still remains extremely puzzling. The aim of this manuscript is to dig into the broad literature on the topic to provide intriguing insights on NO-mediated circuits within immune system. We analysed NO and RNS immunological clues arising from their biochemical properties, immunomodulatory activities and finally dealing with their impact on different pathological scenarios with far prompting intriguing perspectives for their pharmacological targeting.
基金funded by Associazione Italiana per la Ricerca sul Cancro,Milano,Italy(Investigator Grant–IG 2018#21385 to Lara Mussolin),Fondazione Cittàdella Speranza(grant 21/03 to Lara Mussolin)and Fondazione Roche,Roma,Italy(grant“Roche per la ricerca 2018”to Federica Lovisa).
文摘Dear Editor,Anaplastic lymphoma kinase-positive(ALK+)anaplastic large cell lymphoma(ALCL)is an aggressive peripheral Tcell lymphoma representing 10%-15%of pediatric lymphoid neoplasms.The constitutively activated nucleophosmin-ALK(NPM-ALK)fusion protein is the main driver of ALK+ALCL oncogenesis[1].Current clinical protocols can achieve high cure rates,with 75%event-free survival(EFS)at 5 years[2],but the patients’outcome with relapsed/refractory disease still remains poor[3].Liquid biopsy is widely applied for the prognostic and therapeutic stratification of onco-hematological patients.As a non-invasive procedure,it can be used to identify several biomarkers,such as small extracellular vesicles(S-EVs)[4].S-EVs are stable carriers of molecules that mediate genetic exchange between distant cells,alter the microenvironment,facilitate cancer cell progression and promote drug resistance[5].
