Microsatellite Instability in Young Women with Endometrioid type Endometrial Cancer

"nBackground: This study was designed to determine the frequency of Microsatellite Instability (MSI) in young Iranian pa­tients with endometrial carcinoma and to evaluate its association with histopathologic and clinical features of disease."nMethods: Microsatellite status was analyzed in 23 patients with endometrioid type endometrial cancer who were less than 55 years. Clinicopathologic characteristics such as age, International Federation of Gynecology and Obstetric (FIGO) grad­ing and staging of tumor, family history of Hereditary Non-polyposis Colorectal Cancer (HNPCC), oral conception (OC) consump­tion, number of pregnancies, fertility, menstrual cycles and underlying disease were considered. Chi-square and Fisher exact tests were used to find the significant relationships."nResults: MSI analysis showed 8 patients (34.8%) were MSS (Microsatellite Stable), 15 patients (62.5%) were MSI positive. Among cases with MSI phenotype, 4 cases (17.4%) had low instability (MSI-L) and 11 cases (47.8%) had high instability (MSI-H). Three cases with MSI-H had family history of HNPCC related cancers. Five cases (21.7%) had infertility in which 4 of them (80%) had MSI phenotype. There was no statistically significant relationship between MSI phenotype and tumor grade and stage."nConclusion: Few studies reported high frequency of MSI among young patients. Some studies mentioned similar results in endo­metrioid type of tumor. This study showed even higher frequency (65%) when MSI analyzed in young endometrioid type endometrial patients. Most cases with infertility had MSI-H phenotype. It may suggest that beside women with family his­tory of HNPCC, EC screening using MSI would be beneficial in infertile women too. &nbsp

Vaccination with dendritic cells pulsed ex vivo with gp100 peptide-decorated liposomes enhances the efficacy of anti PD-1 therapy in a mouse model of melanoma

Background: Targeting antigens to dendritic cells (DCs) via nanoparticles is a powerful strategy which improves the efficacy of ex vivo antigen-pulsed DC vaccines. Methods: In this study, liposomes were first decorated with gp10025-33 self-antigen and then characterized. Then, DCs were pulsed ex vivo with liposomal gp100 and injected subcutaneously in mice bearing B16F10 established melanoma tumors in combination with anti-PD-1 therapy. Results: Treatment with liposomal pulsed DC vaccine elicited the strongest anticancer immunity and enhanced intratumoral immune responses based on infiltration of gp100-specific CD4+ and CD8+ T cells to the tumor leading to significant tumor growth regression and prolonged survival rate. Treatment with liposomal pulsed DC vaccine also markedly enhanced specific cytotoxic T lymphocytes (CTL) responses with a significant higher titer of IFN-γ in the spleen. Moreover, a significant increase of PD-1 expressing CD8+ tumor infiltrating lymphocytes (TILs) was detected in tumors. Conclusion: Our results demonstrate an optimum dose of liposomal gp100 significantly increases the efficacy of anti-PD-1 therapy in mice and might be an effective strategy to overcome resistance to anti-PD-1 therapy. © 2020 Elsevier Lt