Biology subjects

Binayke, A.

Publications and source records attributed to Binayke, A..

4 recordsLinked to original sources

bioRxiv2025

Cytokine profiling identifies circulating IL-2, IL23 and sPD-L1 as prognostic biomarkers for treatment outcomes in Non-Small cell Lung Cancer patients undergoing anti-PD1 therapy

BackgroundThis study investigates the predictive potential of circulating cytokines for response and survival outcomes in patients with advanced non-small cell lung cancer (NSCLC) undergoing immune checkpoint inhibitor (ICI) therapy. Materials and MethodsA cohort of 64 patients with advanced NSCLC receiving ICI therapy were included. Baseline serum samples were collected prior to ICI initiation and profiled using a multiplex cytokine panel. Logistic regression, Cox regression, and Kaplan-Meier survival analysis were employed to assess associations between cytokine levels, therapeutic response, progression-free survival (PFS), and overall survival (OS). Gene expression levels of key cytokines were validated in peripheral blood mononuclear cells (PBMCs) using quantitative real-time PCR. ResultsElevated baseline levels of IL-2, IL-23, and sPD-L1 were significantly associated with clinical response to ICI therapy. Among these, sPD-L1 emerged as an independent predictor of response (AUC = 0.87). Multivariate Cox regression showed IL-2 (HR = 0.67), sPD-L1 (HR = 0.15), and IL-23 (HR = 1.18) were significantly associated with PFS and also predictive of OS. Notably, combined profiling of IL-2 and sPD-L1 enhanced predictive power (AUC = 0.95 for both PFS and OS). RT-PCR analysis of PBMCs corroborated these findings, confirming upregulation of IL-2 in responders and elevated IL-23 expression in non-responders. ConclusionBaseline cytokine profiling particularly of IL-2, sPD-L1, and IL-23 provides important prognostic and predictive information in advanced NSCLC patients undergoing ICI therapy. These biomarkers may facilitate more personalized approaches to immunotherapy and guide clinical decision-making.

cancer biology↗

bioRxiv2022

Human endogenous retrovirus-R envelope is a host restriction factor against severe acute respiratory syndrome-coronavirus-2

Coronavirus induced disease-19 (COVID-19), caused by the SARS-CoV-2 remains a major global health challenge. Human endogenous retroviruses (HERVs) represent retroviral elements that got integrated into the ancestral human genome. HERVs are important in development and diseases, including cancer, inflammation and viral infections. Here, we analyzed the expression of several HERVs in SARS-CoV-2 infected cells and observed increased activity of HERV-E, HERV-V, HERV-FRD, HERV-MER34, HERV-W and HERV-KHML2. In contrast, HERV-R-envelope was downregulated in cell-based models and COVID-19 patient PBMCs. HERV-R overexpression inhibited SARS-CoV-2 replication, suggesting its antiviral action. Further studies demonstrated the role of extracellular signal-regulated kinase (ERK) in regulating HERV-R antiviral activity. Cross-talk between the ERK and p38 MAPK controls HERV-R envelope synthesis, which in turn modulates the replication of SARS-CoV-2. These findings establish the importance of HERV-R envelope as a host restriction factor against SARS-CoV-2 and illustrate the advantage of integration and evolutionary maintenance of retroviral-elements in the human genome.

microbiology↗

bioRxiv2022

SARS-CoV-2 and its variants, but not Omicron, induces thymic atrophy and impaired T cell development

Pathogenic infections cause thymic atrophy, perturb thymic-T cell development and alter immunological response. Previous studies reported dysregulated T cell function and lymphopenia in coronavirus disease-19 (COVID-19) patients. However, immune-pathological changes, in the thymus, post severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection have not been elucidated. Here, we report SARS-CoV-2 infects thymocytes, depletes CD4+CD8+ (double positive; DP) T cell population associated with an increased apoptosis of thymocytes, which leads to severe thymic atrophy in K18-hACE2-Tg mice. CD44+CD25-T cells were found to be enriched in infected thymus, indicating an early arrest in the T cell developmental pathway. Further, Interferon gamma (IFN-{gamma}) was crucial for thymic atrophy, as anti-IFN-{gamma} antibody neutralization rescued the loss of thymic involution. Therapeutic use of remdesivir (prototype anti-viral drug) was also able to rescue thymic atrophy. While Omicron variant of SARS-CoV2 caused marginal thymic atrophy, delta variant of SARS-CoV-2 exhibited most profound thymic atrophy characterized by severely depleted DP T cells. Recently characterized broadly SARS-CoV-2 neutralizing monoclonal antibody P4A2 was able to rescue thymic atrophy and restore thymic developmental pathway of T cells. Together, we provide the first report of SARS-CoV-2 associated thymic atrophy resulting from impaired T cell developmental pathway and also explains dysregulated T cell function in COVID-19.

immunology↗

bioRxiv2022

Innate immune response and distinct metabolomic signatures together drive and shape the SARS-CoV-2-specific T cell response during COVID-19

The underlying factors contributing to the evolution of SARS-CoV-2-specific T cell responses during COVID-19 infection remain unidentified. To address this, we characterized innate and adaptive immune responses with metabolomic profiling longitudinally at three different time points (0-3, 7-9, and 14-16 days post-COVID-19 positivity) from young mildly symptomatic active COVID-19 patients infected during the first wave in mid-2020. We observed that anti-RBD IgG and viral neutralization are significantly reduced against the Delta variant compared to the ancestral strain. In contrast, compared to the ancestral strain, T cell responses remain preserved against the delta and omicron variants. We determined innate immune responses during the early stage of active infection in response to TLR 3/7/8 mediated activation in PBMCs and serum metabolomic profiling. Correlation analysis indicated PBMCs-derived proinflammatory cytokines, IL-18, IL-1{beta}, and IL-23, and the abundance of plasma metabolites involved in arginine biosynthesis were predictive of a robust SARS-CoV-2-specific Th1 response at a later stage (two weeks after PCR positivity). These observations may contribute to designing effective vaccines and adjuvants that promote innate immune responses and metabolites to induce long-lasting anti-SARS-CoV-2 specific T cells response.

immunology↗