Bacterial RNA downregulates MHC-I in tumor cell lines, promoting NK response and delaying tumor growth
4 affiliations
- 1Instituto de Medicina Experimental-Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Academia Nacional de Medicina, Buenos Aires, Argentina
- 2Centro de Investigaciones Oncológicas-Fundación Cáncer F.U.C.A, Buenos Aires, Argentina
- 3Instituto de Biociencias, Biotecnología y Biología traslacional. Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires, Buenos Aires, Argentina
- 4Universidad Nacional de Río Negro. Instituto de Estudios en Ciencia, Tecnología, Cultura y Desarrollo. Consejo Nacional de Investigaciones Científicas y Técnicas, Río Negro, Argentina
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.
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BibTeX
@article{serafino2026bacterial,
title = {{Bacterial RNA downregulates MHC-I in tumor cell lines, promoting NK response and delaying tumor growth}},
author = {Agustina Serafino and Mónica Vermeulen and Yasmín A. Bertinat and Federico Birnberg-Weiss and Joselyn E. Castro and María Belén Bordignon and Ayelén I. Pesce Viglietti and Jorgelina Bueno and M. Ayelén Milillo and Paula Barrionuevo},
journal = {PLOS One},
year = {2026},
month = sep,
doi = {10.1371/journal.pone.0357999},
url = {https://doi.org/10.1371/journal.pone.0357999},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Bacterial RNA downregulates MHC-I in tumor cell lines, promoting NK response and delaying tumor growth
AU - Agustina Serafino
AU - Mónica Vermeulen
AU - Yasmín A. Bertinat
AU - Federico Birnberg-Weiss
AU - Joselyn E. Castro
AU - María Belén Bordignon
AU - Ayelén I. Pesce Viglietti
AU - Jorgelina Bueno
AU - M. Ayelén Milillo
AU - Paula Barrionuevo
PY - 2026
DA - 2026/09/15
JO - PLOS One
DO - 10.1371/journal.pone.0357999
UR - https://doi.org/10.1371/journal.pone.0357999
AB - 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.
SN - 1932-6203
ER -