Publications by authors named "Emily Robitschek"
The aminopeptidase, endoplasmic reticulum aminopeptidase 1 (ERAP1), trims peptides for loading into major histocompatibility complex class I (MHC class I), and loss of this activity has broad effects on the MHC class I peptidome. Here, we investigated the impact of targeting ERAP1 in immune checkpoint blockade (ICB), as MHC class I interactions mediate both activating and inhibitory functions in antitumor immunity. Loss of ERAP sensitized mouse tumor models to ICB, and this sensitivity depended on CD8 T cells and natural killer (NK) cells.
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- The study revealed that melanoma only formed in zebrafish melanocytes lining internal organs, mirroring the conditions in human patients and highlighting a distinct chromatin structure compared to skin melanomas.
- The findings indicated that zebrafish internal melanocytes share gene expression patterns with human MMs, showing characteristics linked to increased metastasis and decreased response to immunotherapy, thereby providing a valuable model for developing new treatments for MM.
Article Synopsis
- Researchers found a gene called TBK1 that helps cancer cells avoid being attacked by the immune system.
- By blocking TBK1, they made cancer treatments, like PD-1 blockade, more effective.
- Experiments with real patient tumors showed that targeting TBK1 can help kill cancer cells better when combined with certain immune signals.
Epigenetic dysregulation is a defining feature of tumorigenesis that is implicated in immune escape. Here, to identify factors that modulate the immune sensitivity of cancer cells, we performed in vivo CRISPR-Cas9 screens targeting 936 chromatin regulators in mouse tumour models treated with immune checkpoint blockade. We identified the H3K9 methyltransferase SETDB1 and other members of the HUSH and KAP1 complexes as mediators of immune escape.
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- Most melanoma patients eventually stop responding to a type of treatment called immune checkpoint blockade (ICB), so researchers studied one patient’s tumor samples over 9 years.
- They found that different versions of the tumor were changing and adapting in unique ways, making it harder for the treatment to work.
- The study also showed that tumors could behave differently in various parts of the body, with some having more immune cells nearby than others, which can affect how well treatments work.
Most patients with cancer either do not respond to immune checkpoint blockade or develop resistance to it, often because of acquired mutations that impair antigen presentation. Here we show that loss of function of the RNA-editing enzyme ADAR1 in tumour cells profoundly sensitizes tumours to immunotherapy and overcomes resistance to checkpoint blockade. In the absence of ADAR1, A-to-I editing of interferon-inducible RNA species is reduced, leading to double-stranded RNA ligand sensing by PKR and MDA5; this results in growth inhibition and tumour inflammation, respectively.
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