Biology subjects

Ongkeko, W. M.

Publications and source records attributed to Ongkeko, W. M..

3 recordsLinked to original sources

bioRxiv2026

Spatial Neuroimmune Crosstalk Driving Perineural Invasion in Head and Neck Squamous Cell Carcinoma

BackgroundPerineural invasion (PNI) is a clinically important feature of aggressive head and neck squamous cell carcinoma (HNSCC) and is associated with recurrence and poor survival. However, the spatial organization and molecular programs that characterize tumor-nerve interactions in HNSCC remain incompletely understood. MethodsSingle-cell-resolution Xenium spatial transcriptomic data from 10 HNSCC patients were analyzed to define nerve-associated regions, cell-type composition, tumor-nerve proximity, and perineural transcriptional programs. Complementary Visium spatial transcriptomic datasets were used to assess broader transcriptomic features of nerve-associated regions, including epithelial-mesenchymal transition and inferred ligand-receptor signaling. Clinical relevance was evaluated using bulk transcriptomic validation cohorts from TCGA-HNSC and GSE65858. ResultsSpatial mapping identified a distinct nerve-proximal microenvironment characterized by depletion of mature dendritic cells and altered immune and stromal composition, consistent with localized disruption of antigen-presenting support at the tumor-nerve interface. HPV- tumors exhibited closer tumor-nerve proximity and a higher exploratory PNI index compared with HPV+ tumors, suggesting subtype-specific differences in nerve-associated tumor behavior. Differential expression analysis of perineural versus distal tumor cells identified a spatially enriched gene program, including NFE2L2, MDM2, and PPARG, that demonstrated a nerve-proximal gradient most evident in HPV- disease. A composite three-gene score was associated with worse overall survival in HPV- patients in TCGA-HNSC and validated in GSE65858, while showing limited prognostic value in HPV+ disease. Visium analyses provided complementary evidence of EMT enrichment and inferred tumor-nerve signaling involving neural guidance and adhesion-associated pathways. ConclusionsThese findings support a model in which PNI in HNSCC reflects a spatially organized, transcriptionally distinct tumor-nerve microenvironment, particularly in HPV- disease. The NFE2L2/MDM2/PPARG signature may provide a candidate biomarker for risk stratification and nominates pathways for future mechanistic and therapeutic investigation.

cancer biology↗

bioRxiv2026

Evaluation of Alcohol, Tobacco, and HPVs Synergistic regulation of Head and Neck Squamous Cell Carcinoma Treatment Response to PD-L1 Checkpoint Inhibitor Treatment

Although immune checkpoint inhibitors targeting the programmed death-ligand 1 (PD-L1) axis have transformed the treatment of recurrent and metastatic head and neck squamous cell carcinoma (HNSCC), durable clinical responses remain limited to a minority of patients, and the determinants of treatment resistance remain incompletely understood. Human papillomavirus (HPV) infection, alcohol consumption, tobacco use, and are the three most prominent etiological risk factors for HNSCC; however, despite their well-established individual roles in disease development, the influence of their combined exposure on PD-L1 axis regulation and immunotherapy response remains largely unexplored. In this study, we analyzed multi-omic data from 498 primary HNSCC tumors in The Cancer Genome Atlas (TCGA), stratifying patients into seven subgroups reflecting all observed exposure combinations, with HPV status determined directly from RNA-sequencing reads using Pathoscope. Notably, PD-L1 (CD274) expression was significantly downregulated in the triple-exposure cohort (1.51-fold reduction, p < 0.05), along with reduced expression of the upstream regulator JAK2 (1.44-fold reduction, p < 0.05) being seen. Immune deconvolution suggested progressively greater immune infiltration with accumulating exposures, yet gene set enrichment analysis revealed concurrent downregulation of T cell activation, T cell differentiation, and NK cell-mediated immunity in the triple-exposure subgroup -- consistent with an inflamed but functionally suppressed tumor microenvironment. Preliminary integration with an independent single-cell RNA-sequencing dataset of HNSCC patients undergoing neoadjuvant PD-1/CTLA-4 blockade further suggested enrichment of granulocyte and regulatory T cell populations among non-responding patients. Survival differences between cohorts were also observed, likely reflecting biological heterogeneity driven by distinct etiologies and differences in clinical presentation across exposure groups. Together, these findings provide early insights into how multi-etiological exposure burden may shape PD-L1 axis dysregulation and immune microenvironment remodeling in HNSCC, with potential implications for patient stratification in checkpoint inhibitor therapy.

cancer biology↗

bioRxiv2020

Tobacco, but not nicotine and flavor-less electronic cigarettes, induces ACE2 and immune dysregulation

COVID-19, caused by the virus SARS-CoV-2, has infected millions worldwide. This pandemic overlaps with the ongoing epidemics of cigarette smoking and electronic cigarette (e-cig) vaping, with over 1 billion smokers and vapers worldwide. However, there is scarce data relating COVID-19 risks and outcome with cigarette or e-cig use. In this study, we mined 3 independent RNA expression datasets from smokers and vapers to understand the potential relationship between vaping/smoking and the dysregulation of key genes and pathways related to COVID-19. We found that smoking, but not vaping, upregulates ACE2, the cellular receptor that SARS-CoV-2 requires for infection. Both smoking and use of nicotine and flavor-containing e-cig led to upregulations of pro-inflammatory cytokine production and expression of genes related to inflammasomes. Vaping flavor-less and nicotine-less e-cig, however, did not lead to significant cytokine dysregulation and inflammasome activation. Release of inflammasome products, such as IL-1B, and cytokine storms are hallmarks of COVID-19 infection, especially in severe cases. Therefore, our findings demonstrated that smoking or vaping, specifically use of flavored or nicotine-containing e-cigs, may critically exacerbate COVID-19-related inflammation or increase susceptibility to the disease. Further scientific and public health investigations should be undertaken to address these concerning links between COVID-19 and e-cig/smoking.

immunology↗