Expression of Siglec-1,-3,-5 and-10 in porcine cDC1 and cDC2 subsets from blood, spleen and lymph nodes and functional capabilities of these cells
DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY
Authors: Poderoso, T.; Martinez De la Riva, P.; Alvarez, B.; Nieto-Pelegrin, E.; Ezquerra, A.; Dominguez, J.; Revilla, C.
Abstract
Dendritic cells are professional antigen-presenting cells that play a critical role in the development of immune responses. DCs express a variety of Siglecs on their surface, which play a regulatory role modulating their activation through interaction with sialylated structures expressed by cells or pathogens. Here, we characterized the phenotype of porcine conventional dendritic cells subsets from blood, spleen and lymph nodes, emphasizing the analysis of the expression of Siglecs. Siglec-1 was detected in type 1 cDC and, at lower levels, in type 2 cDC in the spleen, being low to negative in blood and lymph node cDC. Siglec-3 and Siglec-5 were expressed in cDC1 at lower levels than in cDC2. Porcine cDCs did not express Siglec-10. cDC2 showed a higher capacity to phagocytose microspheres and to process DQ (TM)-OVA than cDC1, but none of these functions was affected by engagement of Siglec-3 and -5 with antibodies on blood cDC.
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
VACCINE
Authors: Yazdani, Mona; Gholizadeh, Zahra; Nikpoor, Amin Reza; Hatamipour, Mahdi; Alani, Behrang; Nikzad, Hossein; Roshan, Nema Mohamadian; Verdi, Javad; Jaafari, Mahmoud Reza; Noureddini, Mahdi; Badiee, Ali
Abstract
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 gp100(25-33) 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-gamma 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. (C) 2020 Elsevier Ltd. All rights reserved.