Article ; Online: Intratumoral Administration of High-Concentration Nitric Oxide and Anti-mPD-1 Treatment Improves Tumor Regression Rates and Survival in CT26 Tumor-Bearing Mice.
2023 Volume 12, Issue 20
Abstract: Background: Immune checkpoint inhibitors have transformed clinical oncology. However, their use is limited as response is observed in only ~20-50% of patients. Previously, we demonstrated that treating CT26 tumor-bearing mice with ultra-high- ... ...
| Abstract | Background: Immune checkpoint inhibitors have transformed clinical oncology. However, their use is limited as response is observed in only ~20-50% of patients. Previously, we demonstrated that treating CT26 tumor-bearing mice with ultra-high-concentration gaseous nitric oxide (UNO) followed by tumor resection stimulated antitumor immune responses. Accordingly, UNO may improve tumor response to immune checkpoint inhibitors. Here, we investigated the ability of UNO to improve the efficacy of a programmed cell death protein-1 (PD-1) antibody in vitro and in treating CT26 tumor-bearing mice. Methods: CT26 cells were injected into the flank of Balb/c mice ( Results: (1) Short exposure to 25,000-100,000 parts per million (ppm) UNO in vitro resulted in significant upregulation of PD-L1 expression on CT26 cells. (2) UNO treatment in vivo consistently reduced cell viability in CT26 tumors. (3) Treatment reduced regulatory T-cell (Treg) levels in the tumor and increased levels of systemic M1 macrophages. UNO responders had increased CD8+ T-cell tumor infiltration. (4) Nine days after treatment, primary tumor growth was significantly lower in the combination arm vs. anti-mPD-1 alone ( Conclusion: Combining high-concentration NO and immune checkpoint inhibitors warrants further assessment especially in tumors resistant to checkpoint inhibitor therapy. |
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| MeSH term(s) | Humans ; Mice ; Animals ; Nitric Oxide/metabolism ; Immune Checkpoint Inhibitors ; Cell Line, Tumor ; CD8-Positive T-Lymphocytes |
| Chemical Substances | Nitric Oxide (31C4KY9ESH) ; Immune Checkpoint Inhibitors |
| Language | English |
| Publishing date | 2023-10-11 |
| Publishing country | Switzerland |
| Document type | Journal Article ; Research Support, Non-U.S. Gov't |
| ZDB-ID | 2661518-6 |
| ISSN | 2073-4409 ; 2073-4409 |
| ISSN (online) | 2073-4409 |
| ISSN | 2073-4409 |
| DOI | 10.3390/cells12202439 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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