PreprintArticleVersion 1This version is not peer-reviewed
Long-Lasting, Fine-Tuned Anti-tumor Activity of Recombinant Listeria monocytogenes Vaccine Is Controlled by Pyroptosis and Necroptosis Regulatory and Effector Molecules
Version 1
: Received: 11 August 2024 / Approved: 13 August 2024 / Online: 13 August 2024 (11:21:26 CEST)
How to cite:
Olagunju, A. S.; Sardinha, A. V. D.; Amarante-Mendes, G. P. Long-Lasting, Fine-Tuned Anti-tumor Activity of Recombinant Listeria monocytogenes Vaccine Is Controlled by Pyroptosis and Necroptosis Regulatory and Effector Molecules. Preprints2024, 2024080926. https://doi.org/10.20944/preprints202408.0926.v1
Olagunju, A. S.; Sardinha, A. V. D.; Amarante-Mendes, G. P. Long-Lasting, Fine-Tuned Anti-tumor Activity of Recombinant Listeria monocytogenes Vaccine Is Controlled by Pyroptosis and Necroptosis Regulatory and Effector Molecules. Preprints 2024, 2024080926. https://doi.org/10.20944/preprints202408.0926.v1
Olagunju, A. S.; Sardinha, A. V. D.; Amarante-Mendes, G. P. Long-Lasting, Fine-Tuned Anti-tumor Activity of Recombinant Listeria monocytogenes Vaccine Is Controlled by Pyroptosis and Necroptosis Regulatory and Effector Molecules. Preprints2024, 2024080926. https://doi.org/10.20944/preprints202408.0926.v1
APA Style
Olagunju, A. S., Sardinha, A. V. D., & Amarante-Mendes, G. P. (2024). Long-Lasting, Fine-Tuned Anti-tumor Activity of Recombinant Listeria monocytogenes Vaccine Is Controlled by Pyroptosis and Necroptosis Regulatory and Effector Molecules. Preprints. https://doi.org/10.20944/preprints202408.0926.v1
Chicago/Turabian Style
Olagunju, A. S., Andrew V. D. Sardinha and Gustavo P. Amarante-Mendes. 2024 "Long-Lasting, Fine-Tuned Anti-tumor Activity of Recombinant Listeria monocytogenes Vaccine Is Controlled by Pyroptosis and Necroptosis Regulatory and Effector Molecules" Preprints. https://doi.org/10.20944/preprints202408.0926.v1
Abstract
One of the main objectives of developing new anti-cancer vaccine strategies is to effectively induce CD8+ T cell-mediated anti-tumor immunity. Live recombinant vectors, notably Listeria mono-cytogenes, have been shown to elicit a robust in vivo CD8+ T cell response in preclinical settings. Significantly, it has been demonstrated that Listeria induces inflammatory/immunogenic cell death mechanisms such as pyroptosis and necroptosis in immune cells that favorably control immunological responses. Therefore, we postulated that the host's response to Listeria-based vec-tors and the subsequent induction of CD8+ T cell-mediated immunity would be compromised by the lack of regulatory or effector molecules involved in pyroptosis or necroptosis. To test our hy-pothesis, we used recombinant L. monocytogenes carrying the ovalbumin gene (LM.OVA) to vac-cinate wild-type (WT), caspase-1/11-/-, gsdmd-/-, ripk3-/-, and mlkl-/- C57Bl/6 mice. We performed an in vivo cytotoxicity assay to assess the efficacy of OVA-specific CD8+ T lymphocytes in eliminat-ing target cells in wild-type and genetically deficient backgrounds. Furthermore, we evaluated the specific anti-tumor immune response in mice inoculated with B16F0 and B16F0.OVA mela-noma cell lines. Our findings demonstrated that while caspase-1/11 and GSDMD deficiencies in-terfere with the rapid control LM.OVA infection, of the KO seems to contribute to the early acti-vation of OVA-specific CTL responses. In contrast, individual deficiency of each one of these pro-teins negatively impact the generation of long-lasting effector CD8+ T cells.
Keywords
L. monocytogenes, anti-tumor vaccine, CD8 T cell, pyroptosis, necroptosis
Subject
Biology and Life Sciences, Immunology and Microbiology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
