Biology subjects

Quick, C. M.

Publications and source records attributed to Quick, C. M..

3 recordsLinked to original sources

bioRxiv2024

Optical imaging of treatment-naive human NSCLC reveals changes associated with metastatic recurrence

Lung cancer remains the leading cause of cancer deaths, comprising nearly 25% of all cancer deaths [1]. NSCLC accounts for approximately 85% of all cases and encompasses major subtypes such as adenocarcinoma and squamous cell carcinoma. Despite advances in surgical and therapeutic options, NSCLC remains associated with poor prognosis due to a high rate of recurrence, even in early stages. Around 30-55% of patients who undergo complete resection will experience metastatic recurrence, significantly lowering survival outcomes [2]. There is a critical need to develop prognostic markers capable of predicting risk of recurrence at earlier timepoints in order to improve NSCLC management, as it could help clinicians tailor treatment plans, optimize follow-up schedules, and identify high-risk patients who might benefit from adjuvant therapies. Two photon microscopy (TPM) techniques provide non-invasive high-resolution information on cell metabolism within tissue by utilizing an optical redox ratio (ORR) of FAD/[NADH+FAD] autofluorescence. The goal of this study is to use the ORR and NADH fluorescence lifetime decay to identify measurable differences in optical endpoints of human NSCLC that are indicative of their long-term outcome. Twenty-five treatment-naive NSCLC specimens were classified into metastatic and non-metastatic groups according to subject-detail reports. The ORR and mean NADH lifetime were determined for each sample, revealing a significant increase in the ORR for the metastatic group. Additionally, tumors presenting with high optical redox ratios were found to be correlated with low KEAP1, a prognostic indicator of poor clinical outcome in NSCLC. To evaluate the prognostic potential of optical metabolic endpoints, we trained three classifiers: logistic regression, SVM, and KNN on three different feature sets: optical endpoints, clinicopathological features, and combination of optical and clinical features. We found that SVM trained on optical endpoints alone (AUC = 0.74) outperformed the model built with only clinical features (AUC = 0.62), when classifying tumors based on their metastatic recurrence status. Together, these findings highlight the potential of optical metabolic imaging to provide markers of recurrence in NSCLC.

cancer biology↗

bioRxiv2023

BHLHE40 drives protective polyfunctional CD4 T cell differentiation in the female reproductive tract against Chlamydia

The protein basic helix-loop-helix family member e40 (BHLHE40) is a transcription factor recently emerged as a key regulator of host immunity to infections, autoimmune diseases and cancer. In this study, we investigated the role of Bhlhe40 in protective T cell responses to the intracellular bacterium Chlamydia in the female reproductive tract (FRT). Mice deficient in Bhlhe40 exhibited severe defects in their ability to control Chlamydia muridarum shedding from the FRT. The heightened bacterial burdens in Bhlhe40-/-mice correlated with a marked increase in IL-10-producing T regulatory type 1 (Tr1) cells and decreased polyfunctional CD4 T cells co-producing IFN-{gamma}, IL-17A and GM-CSF. Genetic ablation of IL-10 or functional blockade of IL-10R increased CD4 T cell polyfunctionality and partially rescued the defects in bacterial control in Bhlhe40-/- mice. Using single-cell RNA sequencing coupled with TCR profiling, we detected a significant enrichment of stem-like T cell signatures in Bhlhe40-deficient CD4 T cells, whereas WT CD4 T cells were further down on the differentiation trajectory with distinct effector functions beyond IFN-{gamma} production by Th1 cells. Altogether, we identified Bhlhe40 as a key molecular driver of CD4 T cell differentiation and polyfunctional responses in the FRT against Chlamydia.

immunology↗

bioRxiv2020

Expansion of Human Papillomavirus-Specific T Cells in Periphery and Cervix in a Therapeutic Vaccine Recipient Whose Cervical High-Grade Squamous Intraepithelial Lesion Regressed

Advances in high-throughput sequencing have revolutionized the manner with which we can study T cell responses. We describe a woman who received a human papillomavirus (HPV) therapeutic vaccine called PepCan, and experienced complete resolution of her cervical high-grade squamous intraepithelial lesion. By performing bulk T cell receptor (TCR) {beta} deep sequencing of peripheral blood mononuclear cells before and after 4 vaccinations, 70 putatively vaccine-specific clonotypes were identified for being significantly increased using a beta-binomial model. Interferon-{gamma} enzyme-linked immunospot assay identified significantly increased HPV-specific T cell response in the HPV 16 E6 91-115 region after 4 vaccinations (p=0.023). T cells with specificity to this region were sorted and analyzed using single-cell RNA-seq and TCR sequencing, HPV specificity in 60 of the 70 clonotypes identified to be vaccine-specific was demonstrated. TCR {beta} bulk sequencing of the cervical liquid-based cytology samples and cervical formalin-fixed paraffin-embedded samples before and after 4 vaccinations demonstrated the presence of these HPV-specific T cells in the cervix. Combining traditional and cutting-edge immunomonitoring techniques enabled us to demonstrate expansion of HPV-antigen specific T cells in the periphery and cervix.

immunology↗