Bacterial RNA downregulates MHC-I in tumor cell lines, promoting NK response and delaying tumor growth.

Authors

Agustina Serafino, Mónica Vermeulen, Yasmín A Bertinat, Federico Birnberg-Weiss, Joselyn E Castro, María Belén Bordignon, Ayelén I Pesce Viglietti, Jorgelina Bueno, M Ayelén Milillo, Paula Barrionuevo

Published in

PloS one. Volume 21. Issue 9. Pages e0357999. Epub Sep 15, 2026.

Abstract

Immunotherapy has introduced a new era in cancer treatment. The clinical goal of cancer immunotherapy is to prime the host immune system to provide passive or active immunity against malignant tumors. We have previously demonstrated that Brucella abortus (Ba) RNA downregulates IFN-γ-induced MHC-I surface expression in human monocytes/macrophages via a TLR8-dependent mechanism. Other bacterial RNAs can mimic this phenomenon. The presence and activity of NK cells in tumors have been correlated with better patient survival, supporting the evidence that these cells are essential in the immune response against tumors. So, we postulated that bacterial RNA (bacRNA) can be used to modulate MHC-I expression in tumors to enhance the NK cell response. Hence, the aim of this study was to investigate the immunomodulatory role of bacRNA in solid tumors. We first stimulated human glioblastomas U251 and LN-229, colorectal adenocarcinoma HT-29, breast cancer MCF-7, and murine melanoma B16-OVA cells with bacRNA in the presence of IFN-γ. Our experiments demonstrated that bacRNA diminished IFN-γ-induced MHC-I surface expression in all tumor cell lines. Moreover, the hTLR8 agonist ORN06/LyoVec mimicked the effect of bacRNA, indicating that MHC-I reduction would be mediated by TLR8. In addition, the decrease in MHC-I mediated by bacRNA correlated with increased NK cytotoxicity. Finally, treatment with either bacRNA or the ORN06 agonist resulted in greater immune cell infiltration and activation within the tumor compared to untreated mice. Furthermore, bacRNA delayed tumor growth in the B16 melanoma model. Overall, our established model of MHC-I downregulation (either by bacRNA or synthetic hTLR8 agonists) could be used as a therapeutic strategy to promote anti-tumor responses.

PMID:
42743356
Bibliographic data and abstract were imported from PubMed on 16 Sep 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.