Reversal of gastrointestinal carcinoma-induced immunosuppression and induction of antitumoural immunity by a combination of cyclophosphamide and gene transfer of IL-12

Immunotherapy-based strategies for gastrointestinal carcinomas (GIC) have been exploited so far, but these approaches have to face strong mechanisms of immune escape induced by tumours. We previously demonstrated that sub-therapeutic doses of an adenovirus expressing IL-12 genes (AdIL-12) mediated a potent antitumour effect against subcutaneous (s.c.) colorectal carcinomas (CRC) in mice pre-treated with low doses of cyclophosphamide (Cy). In our study we used this combination to assess its impact on the immunosuppressive microenvironment. In s.c. CRC model we demonstrated that non-responder mice failed to decrease Tregs in tumour, spleen and peripheral blood. Reconstitution of Tregs into tumour-bearing mice treated with combined therapy abolished the antitumoural effect. In addition, Cy + AdIL-12 modified Tregs functionality by inhibiting the in vitro secretion of IL-10 and TGF-β and their ability to inhibit dendritic cells activation. Combined treatment decreased the number of myeloid-derived suppressor cells (MDSCs) in comparison to non-treated mice and, interestingly, administration of Tregs restored splenic MDSCs population. Furthermore, combined therapy potently generated specific cytotoxic IFN-γ-secreting CD4+ T cells able to eradicate established CRC tumours after adoptive transfer. Finally, we evaluated the combination on disseminated CRC and pancreatic carcinoma (PC). Cy + AdIL-12 were able to eradicate liver metastatic CRC (47%) and PC tumour nodules (40%) and to prolong animal survival. The results of this study support the hypothesis that Cy + AdIL-12 might be a valid immunotherapeutic strategy for advanced GIC.Fil: Malvicini, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Austral; ArgentinaFil: Ingolotti, Mariana. Universidad Austral; ArgentinaFil: Piccioni, Flavia Valeria. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Austral; ArgentinaFil: García, Mariana Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Austral; ArgentinaFil: Bayo Fina, Juan Miguel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Austral; ArgentinaFil: Atorrasagasti, María Catalina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Austral; ArgentinaFil: Alaniz, Laura Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Austral; ArgentinaFil: Aquino, Jorge Benjamin. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Austral; ArgentinaFil: Espinoza, Jaime A.. Universidad Adolfo Ibañez; Chile. Universidad de La Frontera; ChileFil: Gidekel, Manuel. Universidad Adolfo Ibañez; ChileFil: Scharovsky, Olga Graciela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Medicas. Instituto de Genetica Experimental; ArgentinaFil: Matar, Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Medicas. Instituto de Genetica Experimental; ArgentinaFil: Mazzolini Rizzo, Guillermo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Austral; Argentin

Spectral optical coherence tomography findings in an elderly patient with syphilitic bilateral chronic panuveitis

Purpose: To report the spectral domain optical coherence tomography (SD-OCT) features of a focal retinitis in an elderly male patient with bilateral syphilitic panuveitis. Observations: In the left eye (LE), spectral domain SD-OCT images during the active period revealed hyperreflectivity extending through the full thickness of the retina with no individualization of the layers, except for the retinal pigment epithelium. Once the lesion healed, SD-OCT imaging revealed an inner retinal atrophy and a mild disruption of the retinal pigment epithelium. Conclusions and importance: In our patient, treponemal infection seemed to produce full-thickness retinal damage with partial involvement of the retinal pigment epithelium. The severe retinal damage, in this case, led to a poorer visual outcome than in other forms of syphilitic retinal involvement

Regional Differences in the Clinical Manifestation of Ocular Toxoplasmosis Between the Center and Northeast of Argentina

Purpose: To compare the clinical characteristics of patients with active episodes of ocular toxoplasmosis from three provinces, Misiones, Santa Fe, and Buenos Aires, Argentina. Methods: Patients with a diagnosis of ocular toxoplasmosis from three databases of four tertiary referral uveitis centers were reviewed. Collected data included presentation of the retinochoroiditis, location of the active lesions, associated inflammatory ocular signs and complications. Results: Three hundred thirty-four patients were included in this study. Bilateral involvement of the ocular disease occurred in 26 patients in Misiones (35.14%), 21 patients (12.8%) in Santa Fe, and 9 patients in Buenos Aires (9.4%) (p < 0.001). Extensive retinitis was observed in 49 patients (66.2%) in Misiones, 39 patients (23.8%) in Santa Fe, and 12 patients (12.5%) in Buenos Aires (p < 0.001). Conclusion: The results indicate that there are differences in the clinical characteristics of ocular toxoplasmosis in patients from Misiones, Santa Fe, and Buenos Aires.Fil: Schlaen, Ariel. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina. Hospital Universitario Austral; ArgentinaFil: Colombero, Daniel. Universidad Nacional de Rosario; Argentina. Oftalmologìa Global; ArgentinaFil: Ormaechea, Soledad. Hospital Universitario Austral; ArgentinaFil: Ladeveze, Emilio. Oftalmologìa Global; ArgentinaFil: Rudzinski, Cesar. Rudzinski Oftalmologia; ArgentinaFil: Ingolotti, Mariana. Hospital Universitario Austral; ArgentinaFil: Couto, Cristóbal. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Rudzinski, Marcelo Nicolas. Universidad Catolica de Las Misiones; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Consultorio de Uveitis y Glaucoma; Argentin

Ocular Myasthenia Gravis: AChR Seropositivy and Generalization

Ocular Myasthenia Gravis (OMG) is an autoimmune disorder of the neuromuscular junction characterized by fatigable weakness of extraocular muscles, levator palpebrae, and orbicularis oculi resulting in fatigable ptosis and binocular diplopia. The predominant auto-antibodies in Myasthenia Gravis are, among others, those against acethylcholine receptors. Multiples studies reported a seropositivity between 40% and 60% f or OMG. Some patients may develop weakness in their limbs, bulbar or respiratory muscles,that is, Generalized Myasthenia Gravis (GMG). The purpose of this study is to report the frequency of Acetylcholine Receptor Antibody (AChR) seropositivity i n patients with clinical suspicion of OMG and the percentage of these patients who developed GMG during the follow up