Search Results (2)

Background/Objectives: Immune checkpoint inhibitors have an established role in non-small cell lung cancer (NSCLC) therapy. The loss of HLA-class-I expression allows cancer cell evasion from immune surveillance, disease progression, and failure of immunotherapy. The restoration of HLA-class-I expression may prove to be a game-changer in current immunotherapy strategies. Autophagic activity has been recently postulated to repress HLA-class-I expression in cancer cells. Methods: NSCLC cell lines (A549 and H1299) underwent late-stage (chloroquine and bafilomycin) and early-stage autophagy blockage (ULK1 inhibitors and MAP1LC3A silencing). The HLA-class-I expression was assessed with flow cytometry, a Western blot, and RT-PCR. NSCLC tissues were examined for MAP1LC3A and HLA-class-I expression using double immunohistochemistry. CD8+ T-cell cytotoxicity was examined in cancer cells pre-incubated with chloroquine and anti-PD-L1 monoclonal antibodies (Moabs); Results: A striking increase in HLA-class-I expression following incubation with chloroquine, bafilomycin, and IFNγ was noted in A549 and H1299 cancer cells, respectively. This effect was further confirmed in CD133+ cancer stem cells. HLA-class-I, β2-microglobulin, and TAP1 mRNA levels remained stable. Prolonged exposure to chloroquine further enhanced HLA-class-I expression. Similar results were noted following exposure to a ULK1 and a PIKfyve inhibitor. Permanent silencing of the MAP1LC3A gene resulted in enhanced HLA-class-I expression. In immunohistochemistry experiments, double LC3A+/HLA-class-I expression was seldom. Pre-incubation of H1299 cancer cells with chloroquine and anti-PD-L1 MoAbs increased the mean % of apoptotic/necrotic cells from 2.5% to 18.4%; Conclusions: Autophagy blockers acting either at late or early stages of the autophagic process may restore HLA-class-I-mediated antigen presentation, eventually leading to enhanced immunotherapy efficacy. Full article

Multiple vaccines were developed and administered to immunize people worldwide against SARS-CoV-2 infection. However, changes in platelet count following the course of vaccination have been reported by many studies, suggesting vaccine-induced thrombocytopenia. In this context, designing an effective targeted subunit vaccine with high specificity and efficiency for people with low platelet counts has become a challenge for researchers. Using the in silico-based approaches and methods, the present study explored the antigenic epitopes of the spike protein of SARS-CoV-2 involved in initial binding of the virus with the angiotensin converting enzyme-2 receptor (ACE-2) on the respiratory epithelial cells. The top ten major histocompatibility complex-I (MHC-I) and MHC-II restricted epitopes were found to have 95.26% and 99.99% HLA-class-I population coverage, respectively. Among the top ten promiscuous MHC-I restricted epitopes, ’FTISVTTEI’ had the highest global HLA population coverage of 53.24%, with an antigenic score of 0.85 and a docking score of −162.4 Kcal/mol. The epitope ‘KLNDLCFTNV’ had the best antigenic score of 2.69 and an HLA population coverage of 43.4% globally. The study predicted and documented the most suitable epitopes with the widest global HLA coverage for synthesis of an efficient peptide-based vaccine against the deadly COVID-19. Full article