Biology subjects

Batey, D.

Publications and source records attributed to Batey, D..

3 recordsLinked to original sources

bioRxiv2025

Mapping Lung Cancer Ventilation Dynamics: A Pilot Mouse Study Using Functional Imaging and Lung Mechanics

In vivo models that replicate and reproduce human lung cancer and its response to therapy are necessary for the development of new therapeutic strategies and understanding drug resistance. Imaging lung tumors in live animals to monitor tumor growth and response to therapy is challenging due to the location of the lungs and their constant movement during breathing. Additionally, methods such as computed tomography (CT) only provide structural information and not functional information about how well the lungs are working. X-ray velocimetry (XV) is a novel functional lung imaging technique that generates 3D maps of regional lung expansion during breathing. In other lung diseases it has been shown to provide spatial information on where ventilation changes occur. The aim of this pilot study was to use XV and flexiVent lung mechanics assessments to determine the effect of tumor growth on lung function in mice at 2- or 3-weeks post tumor induction, and to evaluate the efficacy of these two tools. Histological analysis showed that tumour growth was not uniform between animals. At 3-weeks post tumor induction, some XV ventilation and flexiVent lung mechanics parameters were significantly different from baseline metrics. In addition, the forced expiratory volume, small-scale ventilation heterogeneity, and the average CT gray value correlated with the tumour counts from the histology. In some mice XV revealed localised regions with altered expansion rates. This pilot study demonstrated that changes in lung function can be identified following tumor induction, and that the model and techniques could be used in the future to determine response to anti-tumor drugs.

biophysics↗

bioRxiv2024

Myeloid-instructed CD14+CD4+ T cells within the tumor microenvironment are associated with TNFα signaling and prolonged survival in non-small cell lung cancer

The tumor microenvironment (TME) harbors a diverse array of innate and adaptive immune cells that can either support anti-tumor immunity or facilitate tumor progression. Among these, myeloid cells are key drivers of immunosuppression, yet therapeutic strategies targeting their function have achieved limited clinical success. A deeper understanding of the mechanisms by which immunosuppressive myeloid cells promote tumor progression is needed to guide the development of more effective treatments. Using spatial multi-omics analyses, we identified a population of myeloid-instructed CD14+ T cells present in both the tumor core and adjacent non-malignant lung tissue of patients with non-small cell lung cancer (NSCLC). CD4+ T cells acquired CD14 from myeloid cells by trogocytosis, resulting in an atypical T cell phenotype. High infiltration of CD14+CD4+ T cells in the tumor core was associated with poor patient survival. Spatial transcriptomics profiling revealed that tumors enriched in CD14+CD4+ T cells exhibited increased TNF signaling. Functional assays demonstrated that TNF enhanced trogocytosis, promoting the transfer of myeloid membrane components to CD4{square} T cells and driving the accumulation of CD14{square}CD4{square} T cells. These findings uncover a novel TNF-mediated mechanism of immunosuppression in the TME, whereby TNF promotes aberrant myeloid-T cell interactions that may contribute to tumor progression. This work highlights a previously unrecognized axis of innate-adaptive immune crosstalk in NSCLC and suggests that targeting TNF could disrupt this pathway, restore effective T cell function, and improve therapeutic outcomes.

cancer biology↗

bioRxiv2021

Early immune pressure imposed by tissue resident memory T cells sculpts tumour evolution in non-small cell lung cancer

Tissue-resident memory T cells (TRM) provide immune defence against local infection and can inhibit cancer progression. However, it is unclear to what extent chronic inflammation impacts TRM activation and how the immune pressure exerted by TRM affects developing tumours in humans. We performed deep profiling of lung cancers arising in never-smokers (NS) and ever-smokers (ES), finding evidence of enhanced TRM immunosurveillance in ES lung. Only tumours arising in ES patients underwent clonal immune escape, even when evaluating cancers with similar tumour mutational burden to NS patients, suggesting that the timing of immune pressure exerted by TRM is a critical factor in the evolution of tumour immune evasion. Tumours grown in T cell quiescent NS lungs displayed little evidence of immune evasion and had fewer neoantigens with low diversity, paradoxically making them amenable to treatment with agonist of the costimulatory molecule, ICOS. These data demonstrate local environmental insults enhance TRM immunosurveillance of human tissue, shape the evolution of tumour immunogenicity and that this interplay informs effective immunotherapeutic modalities.

cancer biology↗