Kevin Litchfield

2 months ago | biorxiv.org | Kunal Shah |Paul Kennedy |James Black |Kevin Litchfield

AbstractLIMD1 is a tumour suppressor gene frequently lost in non-small cell lung cancer (NSCLC), but its role in cancer-immune cell interactions remains unexplored. Here, we demonstrate that LIMD1 loss results in upregulation of the key immune checkpoint protein PD-L1. Using multi-region sequencing from the TRACERx dataset, we identify that LIMD1 loss is clonal in over 80% of squamous cell carcinoma (LUSC) and 40% of lung adenocarcinoma (LUAD) cases, correlating with increased PD-L1 expression.

Jul 14, 2024 | nature.com | Richard Culliford |Charlie Mills |Alex J. Cornish |Ben Kinnersley |Amit Sud |Husayn Pallikonda | +5 more

AbstractClear cell renal cell carcinoma (ccRCC) is the most common form of kidney cancer, but a comprehensive description of its genomic landscape is lacking. We report the whole genome sequencing of 778 ccRCC patients enrolled in the 100,000 Genomes Project, providing for a detailed description of the somatic mutational landscape of ccRCC.

May 31, 2024 | nature.com | Robert Hynds |Ariana Huebner |David Pearce |Mark Hill |Ayse U. Akarca |David Moore | +17 more

AbstractPatient-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.

May 22, 2023 | nature.com | Aaron Javitt |Merav D. Shmueli |Matthias P. Kramer |Aleksandra A. Kolodziejczyk |Kevin Litchfield |Adi Ulman | +7 more

AbstractImmunotherapy revolutionized treatment options in cancer, yet the mechanisms underlying resistance in many patients remain poorly understood. Cellular proteasomes have been implicated in modulating antitumor immunity by regulating antigen processing, antigen presentation, inflammatory signaling and immune cell activation. However, whether and how proteasome complex heterogeneity may affect tumor progression and the response to immunotherapy has not been systematically examined.