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  4. Inhibition of anti-tumor immunity by melanoma cell-derived Activin-A depends on STING
 
research article

Inhibition of anti-tumor immunity by melanoma cell-derived Activin-A depends on STING

Pinjusic, Katarina  
•
Ambrosini, Giovanna  
•
Lourenco, Joao
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January 18, 2024
Frontiers In Immunology

The transforming growth factor-beta (TGF-beta) family member activin A (hereafter Activin-A) is overexpressed in many cancer types, often correlating with cancer-associated cachexia and poor prognosis. Activin-A secretion by melanoma cells indirectly impedes CD8+ T cell-mediated anti-tumor immunity and promotes resistance to immunotherapies, even though Activin-A can be proinflammatory in other contexts. To identify underlying mechanisms, we here analyzed the effect of Activin-A on syngeneic grafts of Braf mutant YUMM3.3 mouse melanoma cells and on their microenvironment using single-cell RNA sequencing. We found that the Activin-A-induced immune evasion was accompanied by a proinflammatory interferon signature across multiple cell types, and that the associated increase in tumor growth depended at least in part on pernicious STING activity within the melanoma cells. Besides corroborating a role for proinflammatory signals in facilitating immune evasion, our results suggest that STING holds considerable potential as a therapeutic target to mitigate tumor-promoting Activin-A signaling at least in melanoma.

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Type
research article
DOI
10.3389/fimmu.2023.1335207
Web of Science ID

WOS:001153644900001

Author(s)
Pinjusic, Katarina  
Ambrosini, Giovanna  
Lourenco, Joao
Fournier, Nadine
Iseli, Christian  
Guex, Nicolas  
Egorova, Olga  
Nassiri, Sina
Constam, Daniel B  
Date Issued

2024-01-18

Publisher

Frontiers Media Sa

Published in
Frontiers In Immunology
Volume

14

Article Number

1335207

Subjects

Life Sciences & Biomedicine

•

Cancer

•

Intercellular Communication

•

Scrna-Seq

•

Profiling

•

Knockdown

•

Activin

•

Interferon

•

Sting

Editorial or Peer reviewed

REVIEWED

Written at

EPFL

EPFL units
UPCDA  
BICC  
FunderGrant Number

Oncosuisse10.13039/501100004201

Available on Infoscience
February 23, 2024
Use this identifier to reference this record
https://infoscience.epfl.ch/handle/20.500.14299/205435
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