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- Title
Gaseous nitric oxide tumor ablation induces an anti-tumor abscopal effect.
- Authors
Confino, Hila; Dirbas, Frederick M.; Goldshtein, Matan; Yarkoni, Shay; Kalaora, Rinat; Hatan, Meital; Puyesky, Shani; Levi, Yakir; Malka, Lidor; Johnson, Matt; Chaisson, Selena; Monson, Jedidiah M.; Avniel, Amir; Lisi, Steve; Greenberg, David; Wolf, Ido
- Abstract
Background: In-situ tumor ablation provides the immune system with the appropriate antigens to induce anti-tumor immunity. Here, we present an innovative technique for generating anti-tumor immunity by delivering exogenous ultra-high concentration (> 10,000 ppm) gaseous nitric oxide (UHCgNO) intratumorally. Methods: The capability of UHCgNO to induce apoptosis was tested in vitro in mouse colon (CT26), breast (4T1) and Lewis lung carcinoma (LLC-1) cancer cell lines. In vivo, UHCgNO was studied by treating CT26 tumor-bearing mice in-situ and assessing the immune response using a Challenge assay. Results: Exposing CT26, 4T1 and LLC-1 cell lines to UHCgNO for 10 s–2.5 min induced cellular apoptosis 24 h after exposure. Treating CT26 tumors in-situ with UHCgNO followed by surgical resection 14 days later resulted in a significant secondary anti-tumor effect in vivo. 100% of tumor-bearing mice treated with 50,000 ppm UHCgNO and 64% of mice treated with 20,000 ppm UHCgNO rejected a second tumor inoculation, compared to 0% in the naive control for 70 days. Additionally, more dendrocytes infiltrated the tumor 14 days post UHCgNO treatment versus the nitrogen control. Moreover, T-cell penetration into the primary tumor was observed in a dose-dependent manner. Systemic increases in T- and B-cells were seen in UHCgNO-treated mice compared to nitrogen control. Furthermore, polymorphonuclear-myeloid-derived suppressor cells were downregulated in the spleen in the UHCgNO-treated groups. Conclusions: Taken together, our data demonstrate that UHCgNO followed by the surgical removal of the primary tumor 14 days later induces a strong and potent anti-tumor response.
- Subjects
NITRIC oxide; SUPPRESSOR cells; CELL lines; SURGICAL excision; TUMORS
- Publication
Cancer Cell International, 2022, Vol 22, Issue 1, p1
- ISSN
1475-2867
- Publication type
Article
- DOI
10.1186/s12935-022-02828-z