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MHC Hammer reveals genetic and non-genetic HLA disruption in cancer evolution.
Nat Genet
October 2024
Cancer Genome Evolution Research Group, Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.
Disruption of the class I human leukocyte antigen (HLA) molecules has important implications for immune evasion and tumor evolution. We developed major histocompatibility complex loss of heterozygosity (LOH), allele-specific mutation and measurement of expression and repression (MHC Hammer). We identified extensive variability in HLA allelic expression and pervasive HLA alternative splicing in normal lung and breast tissue.
View Article and Find Full Text PDFRepresentation of genomic intratumor heterogeneity in multi-region non-small cell lung cancer patient-derived xenograft models.
Nat Commun
May 2024
Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.
Patient-derived xenograft (PDX) models are widely used in cancer research. To investigate the genomic fidelity of non-small cell lung cancer PDX models, we established 48 PDX models from 22 patients enrolled in the TRACERx study. Multi-region tumor sampling increased successful PDX engraftment and most models were histologically similar to their parent tumor.
View Article and Find Full Text PDFInterplay in galectin expression predicts patient outcomes in a spatially restricted manner in PDAC.
Biomed Pharmacother
March 2024
Institute of Inflammation and Ageing, University of Birmingham, Birmingham B15 2TT, UK. Electronic address:
Background: Galectins (Gal's) are a family of carbohydrate-binding proteins that are known to support the tumour microenvironment through their immunosuppressive activity and ability to promote metastasis. As such they are attractive therapeutic targets, but little is known about the cellular expression pattern of galectins within the tumour and its neighbouring stromal microenvironment. Here we investigated the cellular expression pattern of Gals within pancreatic ductal adenocarcinoma (PDAC).
View Article and Find Full Text PDFSpatial determination and prognostic impact of the fibroblast transcriptome in pancreatic ductal adenocarcinoma.
Elife
June 2023
Institute of Immunology and Immunotherapy, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom.
Pancreatic ductal adenocarcinoma has a poor clinical outcome and responses to immunotherapy are suboptimal. Stromal fibroblasts are a dominant but heterogenous population within the tumor microenvironment and therapeutic targeting of stromal subsets may have therapeutic utility. Here, we combine spatial transcriptomics and scRNA-Seq datasets to define the transcriptome of tumor-proximal and tumor-distal cancer-associated fibroblasts (CAFs) and link this to clinical outcome.
View Article and Find Full Text PDFTracking early lung cancer metastatic dissemination in TRACERx using ctDNA.
Nature
April 2023
Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.
Circulating tumour DNA (ctDNA) can be used to detect and profile residual tumour cells persisting after curative intent therapy. The study of large patient cohorts incorporating longitudinal plasma sampling and extended follow-up is required to determine the role of ctDNA as a phylogenetic biomarker of relapse in early-stage non-small-cell lung cancer (NSCLC). Here we developed ctDNA methods tracking a median of 200 mutations identified in resected NSCLC tissue across 1,069 plasma samples collected from 197 patients enrolled in the TRACERx study.
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