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| Status |
Public on Oct 08, 2024 |
| Title |
Identification of cathepsin L as an inter-organ target to mitigate cachexia while enhancing tumor suppression by anti-PD-L1 [TA] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Immune checkpoint inhibitors (ICIs) can induce immune-related adverse events (irAEs) due to an overly activated immune system, despite their anti-cancer effects. Here, we observe that ICI treatment is associated with body weight loss in cancer patients. Similarly, anti-PD-L1 exacerbates muscle wasting in cancer cachexia (CAC) mice, despite its tumor suppressive effects, suggesting muscle atrophy as a potential irAE. Notably, CD8+ T cells accumulate in the skeletal muscle of CAC mice, which is amplified by anti-PD-L1. These CD8+ T cells directly promote muscle wasting, but their depletion effectively prevents cachectic features in CAC mice. We identify cathepsin L (CTSL) as an inter-organ target capable of suppressing both cancer and muscle wasting, particularly that driven by CD8+ T cells. Indeed, CTSL blockade effectively mitigates muscle wasting and further enhances the anti-tumor activity of anti-PD-L1. Thus, CTSL represents a dual therapeutic target for both cancer and cachexia, offering the potential to prevent muscle-related irAE when combined with ICIs.
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| Overall design |
To identify effective therapeutic targets for both cachexia and muscle-related immune-related adverse events (irAEs), we generated RNA-seq data from fromtibialis anterior (TA) muscles in a cancer cachexia mouse model treated with IgG, anti-PD-L1, and anti-CD8a
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| Contributor(s) |
Song N, Lee H |
| Citation missing |
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| |
| Submission date |
Sep 30, 2024 |
| Last update date |
Oct 08, 2024 |
| Contact name |
Haeseung Lee |
| E-mail(s) |
haeseung@pusan.ac.kr
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| Organization name |
Pusan National University
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| Department |
College of Pharmacy
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| Street address |
63 Beon-gil 2, Busandaehag-ro, Geumjeong-gu
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| City |
Busan |
| ZIP/Postal code |
46241 |
| Country |
South Korea |
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| Platforms (1) |
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| Samples (15)
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| Relations |
| BioProject |
PRJNA1167182 |
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