Systemic administration of imiquimod as an adjuvant improves immunogenicity of a tumor-lysate vaccine inducing the rejection of a highly aggressive T-cell lymphoma

T-cell lymphomas include diverse malignancies. They are rare, some have low survival rates and they lack curative therapies. The aim of this work was to assess whether employing the TLR7 agonist imiquimod and the T-cell costimulatory molecule CD40 or the combination of both as adjuvants of a cell lysate vaccine could enhance the antitumor immune response using a murine T-cell lymphoma model. Immunization with LBC-lysate and imiquimod protected almost all vaccinated animals. A specific humoral and a Th1-type cellular immunity were induced in mice that rejected the lymphoma, characterized by an elevated number of CD4 + T-cells and secretion of IFN-γ, locally and systemically. In contrast, CD40 alone or in combination with imiquimod did not improve the protective response obtained with LBC-lysate and imiquimod. Systemic administration of imiquimod proved to have high potential to serve as a vaccine adjuvant for the treatment of T-cell lymphomas and was effective in this immunotherapy model.Fil: Di Sciullo, Maria Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; ArgentinaFil: Menay, Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; ArgentinaFil: Cocozza, Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; ArgentinaFil: Gravisaco, María José. Instituto Nacional de Tecnología Agropecuaria; ArgentinaFil: Waldner, Claudia Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; ArgentinaFil: Mongini, Claudia. Instituto Nacional de Tecnología Agropecuaria; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; Argentin

Exosomes Isolated from Ascites of T-Cell Lymphoma-Bearing Mice Expressing Surface CD24 and HSP-90 Induce a Tumor-Specific Immune Response

Extracellular vesicles (EVs), including endosome-derived nanovesicles (exosomes), are involved in cell–cell communication. Through transfer of their molecular contents, extracellular nanovesicles can alter the function of recipient cells. Due to these characteristics, EVs have shown potential as a new alternative for cancer immunotherapy. Tumor exosomes isolated from malignant ascites can activate dendritic cells, thereby priming the immune system to recognize and kill cancer cells. However, a suppressive role on tumor immune response has also been reported, suggesting that the neoplastic stage of carcinogenesis and the microenvironment where tumor cells grow may influence the amount of EVs released by the cell. This neoplastic stage and microenvironment may also impact EVs’ components such as proteins and miRNA, determining their biological behavior. Most T-cell lymphomas have an aggressive clinical course and poor prognosis. Consequently, complementary alternative therapies are needed to improve the survival rates achieved with conventional treatments. In this work, we have characterized EVs isolated from ascites of mice bearing a very aggressive murine T-cell lymphoma and have studied their immunogenic properties. Small EVs were isolated by differential centrifugation, ultrafiltration, and ultracentrifugation at 100,000 × g on a sucrose cushion. The EVs were defined as exosomes by their morphology and size analyzed by electron microscopy, their floating density on a sucrose gradient, as well as their expression of endosome marker proteins ALIX, TSG-101; the tetraspanins CD63, CD9, and CD81. In addition, they contain tumor antigens, the marker for malignancy CD24, the heat shock protein HSP-70, and an unusual surface expression of HSP-90 was demonstrated. The administration of EVs isolated from ascites (EVs A) into naïve-syngeneic mice induced both humoral and cellular immune responses that allowed the rejection of subsequent tumor challenges. However, the immunization had no effect on a non-related mammary adenocarcinoma, demonstrating that the immune response elicited was specific and also it induced immune memory. In vitro analysis demonstrated that T-cells from EVs A-immunized mice secrete IFN-γ in response to tumor stimulation. Furthermore, tumor-specific CD4+ and CD8+ IFN-γ secreting cells could be efficiently expanded from mice immunized with EVs A, showing that a T helper 1 response is involved in tumor rejection. Our findings confirm exosomes as promising defined acellular tumor antigens for the development of an antitumor vaccine.Inst. de BiotecnologíaFil: Menay, Florencia. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Estudios Farmacológicos y Botánicos; Argentina. Universidad de Buenos. Facultad de Medicina, Aires; ArgentinaFil: Herschlik, Leticia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Estudios Farmacológicos y Botánicos; Argentina. Universidad de Buenos. Facultad de Medicina, Aires; ArgentinaFil: Cocozza, Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Estudios Farmacológicos y Botánicos; Argentina. Universidad de Buenos. Facultad de Medicina, Aires; ArgentinaFil: Tsacalian, Rodrigo Farid. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Estudios Farmacológicos y Botánicos; Argentina. Universidad de Buenos. Facultad de Medicina, Aires; ArgentinaFil: Gravisaco, Marí­a José. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Biotecnología; ArgentinaFil: Di Sciullo, Maria Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Estudios Farmacológicos y Botánicos; Argentina. Universidad de Buenos. Facultad de Medicina; ArgentinaFil: Vendrell, Alejandrina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Estudios Farmacológicos y Botánicos; Argentina. Universidad de Buenos. Facultad de Medicina, Aires; ArgentinaFil: Waldner, Claudia Inés. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Estudios Farmacológicos y Botánicos; Argentina. Universidad de Buenos. Facultad de Medicina, Aires; ArgentinaFil: Mongini, Claudia. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Estudios Farmacológicos y Botánicos; Argentina. Universidad de Buenos. Facultad de Medicina; Argentin

Interventional Radiological Management and Prevention of Complications after Pancreatic Surgery: Drainage, Embolization and Islet Auto-Transplantation

Pancreatic surgery still remains burdened by high levels of morbidity and mortality with a relevant incidence of complications, even in high volume centers. This review highlights the interventional radiological management of complications after pancreatic surgery. The current literature regarding the percutaneous drainage of fluid collections due to pancreatic fistulas, percutaneous transhepatic biliary drainage due to biliary leaks and transcatheter embolization (or stent–graft) due to arterial bleeding is analyzed. Moreover, also, percutaneous intra-portal islet auto-transplantation for the prevention of pancreatogenic diabetes in case of extended pancreatic resection is also examined. Moreover, a topic not usually treated in other similar reviewsas percutaneous intra-portal islet autotransplantation for the prevention of pancreatogenic diabetes in case of extended pancreatic resection is also one of our areas of focus. In islet auto-transplantation, the patient is simultaneously donor and recipient. Differently from islet allo-transplantation, it does not require immunosuppression, has no risk of rejection and is usually efficient with a small number of transplanted islets

Governance e Risk Culture

Il Position Paper Governance e Risk Culture di AIFIRM affronta in modo organico il tema “risk culture & culture risk”, delineando una visione olistica che integra prospettive regolamentari, organizzative e operative. Il documento esordisce chiarendo la differenza fra risk culture – l’insieme di valori, norme e comportamenti che orientano l’assunzione consapevole dei rischi – e culture risk, ossia il rischio generato da un divario fra i principi dichiarati e le pratiche effettive dell’organizzazione. Senza una solida cultura del rischio, il culture risk diventa un fattore potenzialmente letale per la sostenibilità dell’intermediario. Sul piano normativo-regolamentare viene ricostruita l’evoluzione europea: dalle Linee guida BCBS/FSB fino alla ECB Draft Guide on Governance & Risk Culture (luglio 2024). La supervisione si attende oggi che la cultura del rischio sia misurabile, verificabile e proporzionata a dimensione, complessità e modello di business. Particolare enfasi è posta sui quattro “pillar” individuati dalla ECB – tone from the top, comunicazione & challenge, accountability e incentivi – cui l’intervento del Regolatore affianca la declinazione di indicatori di “red flag” utili al monitoraggio. Ampio spazio è dedicato alla governance. Il Board, supportato dai Comitati e dalle Funzioni di Controllo, deve guidare la diffusione della cultura del rischio, garantendo indipendenza di giudizio, adeguata composizione collettiva e presidio di competenze ESG/ICT. La funzione Risk Management assume un ruolo trasversale: dalla definizione del Risk Appetite Statement al presidio dei framework di KPI/KRI. Compliance e Internal Audit completano le “tre linee di difesa”, assicurando rispettivamente conformità exante e assurance indipendente ex-post. Sul versante operativo il paper dettaglia processi di identificazione, misurazione, monitoraggio e reporting, evidenziando la necessità di: • sistemi dati integrati e affidabili (data-governance); • formazione estesa e modulare mirata a elevare la risk awareness; • meccanismi di escalation chiari, supportati da canali di whistleblowing. Viene inoltre proposta una matrice di proporzionalità che calibra struttura di governance, intensità dei controlli e copertura culturale rispetto a quattro profili di banca (LSI, domestica complessa, gruppo internazionale, fintech-driven). In sintesi, il documento individua nella cultura del rischio non un mero obbligo regolamentare bensì un vantaggio competitivo: solo integrando risk culture e performance management un intermediario può coniugare crescita, innovazione e resilienza di lungo periodo, preservando fiducia di clienti, investitori e vigilanza

Acute diverticulitis management: evolving trends among Italian surgeons. A survey of the Italian Society of Colorectal Surgery (SICCR)

Acute diverticulitis (AD) is associated with relevant morbidity/mortality and is increasing worldwide, thus becoming a major issue for national health systems. AD may be challenging, as clinical relevance varies widely, ranging from asymptomatic picture to life-threatening conditions, with continuously evolving diagnostic tools, classifications, and management. A 33-item-questionnaire was administered to residents and surgeons to analyze the actual clinical practice and to verify the real spread of recent recommendations, also by stratifying surgeons by experience. CT-scan remains the mainstay of AD assessment, including cases presenting with recurrent mild episodes or women of child-bearing age. Outpatient management of mild AD is slowly gaining acceptance. A conservative management is preferred in non-severe cases with extradigestive air or small/non-radiologically drainable abscesses. In severe cases, a laparoscopic approach is preferred, with a non-negligible number of surgeons confident in performing emergency complex procedures. Surgeons are seemingly aware of several options during emergency surgery for AD, since the rate of Hartmann procedures does not exceed 50% in most environments and damage control surgery is spreading in life-threatening cases. Quality of life and history of complicated AD are the main indications for delayed colectomy, which is mostly performed avoiding the proximal vessel ligation, mobilizing the splenic flexure and performing a colorectal anastomosis. ICG is spreading to check anastomotic stumps' vascularization. Differences between the two experience groups were found about the type of investigation to exclude colon cancer (considering the experience only in terms of number of colectomies performed), the size of the peritoneal abscess to be drained, practice of damage control surgery and the attitude towards colovesical fistula

Acute diverticulitis management: evolving trends among Italian surgeons. A survey of the Italian Society of Colorectal Surgery (SICCR)

Acute diverticulitis (AD) is associated with relevant morbidity/mortality and is increasing worldwide, thus becoming a major issue for national health systems. AD may be challenging, as clinical relevance varies widely, ranging from asymptomatic picture to life-threatening conditions, with continuously evolving diagnostic tools, classifications, and management. A 33-item-questionnaire was administered to residents and surgeons to analyze the actual clinical practice and to verify the real spread of recent recommendations, also by stratifying surgeons by experience. CT-scan remains the mainstay of AD assessment, including cases presenting with recurrent mild episodes or women of child-bearing age. Outpatient management of mild AD is slowly gaining acceptance. A conservative management is preferred in non-severe cases with extradigestive air or small/non-radiologically drainable abscesses. In severe cases, a laparoscopic approach is preferred, with a non-negligible number of surgeons confident in performing emergency complex procedures. Surgeons are seemingly aware of several options during emergency surgery for AD, since the rate of Hartmann procedures does not exceed 50% in most environments and damage control surgery is spreading in life-threatening cases. Quality of life and history of complicated AD are the main indications for delayed colectomy, which is mostly performed avoiding the proximal vessel ligation, mobilizing the splenic flexure and performing a colorectal anastomosis. ICG is spreading to check anastomotic stumps’ vascularization. Differences between the two experience groups were found about the type of investigation to exclude colon cancer (considering the experience only in terms of number of colectomies performed), the size of the peritoneal abscess to be drained, practice of damage control surgery and the attitude towards colovesical fistula