Version 1
: Received: 1 May 2024 / Approved: 2 May 2024 / Online: 2 May 2024 (12:04:27 CEST)
How to cite:
Nanajian, A.; Scott, M.; Burcus, N. I.; Ruedlinger, B. L.; Oshin, A.; Beebe, S. J.; Guo, S. Nano-Pulse Treatment Overcomes Immunosuppressive Tumor Microenvironment to Elicit In Situ Vaccination Protection against Breast Cancer. Preprints2024, 2024050092. https://doi.org/10.20944/preprints202405.0092.v1
Nanajian, A.; Scott, M.; Burcus, N. I.; Ruedlinger, B. L.; Oshin, A.; Beebe, S. J.; Guo, S. Nano-Pulse Treatment Overcomes Immunosuppressive Tumor Microenvironment to Elicit In Situ Vaccination Protection against Breast Cancer. Preprints 2024, 2024050092. https://doi.org/10.20944/preprints202405.0092.v1
Nanajian, A.; Scott, M.; Burcus, N. I.; Ruedlinger, B. L.; Oshin, A.; Beebe, S. J.; Guo, S. Nano-Pulse Treatment Overcomes Immunosuppressive Tumor Microenvironment to Elicit In Situ Vaccination Protection against Breast Cancer. Preprints2024, 2024050092. https://doi.org/10.20944/preprints202405.0092.v1
APA Style
Nanajian, A., Scott, M., Burcus, N. I., Ruedlinger, B. L., Oshin, A., Beebe, S. J., & Guo, S. (2024). Nano-Pulse Treatment Overcomes Immunosuppressive Tumor Microenvironment to Elicit In Situ Vaccination Protection against Breast Cancer. Preprints. https://doi.org/10.20944/preprints202405.0092.v1
Chicago/Turabian Style
Nanajian, A., Stephen J. Beebe and Siqi Guo. 2024 "Nano-Pulse Treatment Overcomes Immunosuppressive Tumor Microenvironment to Elicit In Situ Vaccination Protection against Breast Cancer" Preprints. https://doi.org/10.20944/preprints202405.0092.v1
Abstract
We previously reported nano-pulse treatment (NPT), a pulsed power technology, resulted in 4T1-luc mammary tumor elimination and a strong in situ vaccination, thereby completely protecting tumor-free animals against a second live tumor challenge. The mechanism whereby NPT mounts effective antitumor immune responses in the 4T1 breast cancer predominantly immunosuppressive tumor microenvironment (TME) remains unanswered. In this study, orthotopic 4T1 mouse breast tumors were treated with NPT (100 ns, 50 kV/cm, 1000 pulses, 3 Hz). Blood, spleen, draining lymph nodes and tumors were harvested at 4-hour, 8-hour, 1-, 3-, 7-day. Additional studies were conducted over 3-month posttreatment intervals for the analysis of frequencies, death and functional markers of various immune cells in addition to suppressor function of regulatory T cells (Tregs). NPT was verified to elicit strong in situ vaccination (ISV) against breast cancer and promoted both acute and long-term T cell memory. NPT abolished immunosuppressive dominance systemically and in the TME by substantially reducing Tregs, myeloid-derived suppressor cells (MDSCs), and tumor-associated macrophages (TAMs). NPT induced apoptosis in Tregs and TAMs. It also functionally diminished the Treg suppression capacity, likely explained by the downregulation of activation markers, particularly 4-1BB and TGFβ, and a phenotypic shift from predominantly activated (CD44+CD62L-) to naïve (CD44-CD62L+) Tregs. Importantly, NPT selectively induced apoptosis in activated Tregs and spared effector CD4+ and CD8+ T cells. These changes were followed by a concomitant rise in CD8+CD103+ tissue-resident memory T cells and TAM M1 polarization. These findings indicate that NPT effectively switches the TME and secondary lymphatic systems from an immunosuppressive to an immunostimulatory state allowing cytotoxic T-cell function and immune memory formation to eliminate cancer cells and account for the NPT in situ vaccination.
Keywords
Nano-pulse treatment (NPT); in situ vaccination; breast cancer; tumor microenvironment; immunosuppression; apoptosis; memory T cells; regulatory T cells; myeloid-derived suppressor cells; tumor-associated macrophages
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.
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