Hyperdifferentiated murine melanoma cells promote adaptive anti-tumor immunity but activate the immune checkpoint system
Accumulating evidence suggests that phenotype switching of cancer cells is essential for therapeutic resistance. However, the immunological characteristics of drug-induced phenotype-switching melanoma cells (PSMCs) are unknown. We investigated PSMC elimination by host immunity using hyperdifferentia...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2025-12-01
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| Series: | OncoImmunology |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/2162402X.2024.2437211 |
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| author | Yukie Ando Yutaka Horiuchi Sara Hatazawa Momo Mataki Akihiro Nakamura Takashi Murakami |
| author_facet | Yukie Ando Yutaka Horiuchi Sara Hatazawa Momo Mataki Akihiro Nakamura Takashi Murakami |
| author_sort | Yukie Ando |
| collection | DOAJ |
| description | Accumulating evidence suggests that phenotype switching of cancer cells is essential for therapeutic resistance. However, the immunological characteristics of drug-induced phenotype-switching melanoma cells (PSMCs) are unknown. We investigated PSMC elimination by host immunity using hyperdifferentiated melanoma model cells derived from murine B16F10 melanoma cells. Exposure of B16F10 cells to staurosporine induced a hyperdifferentiated phenotype associated with transient drug tolerance. Staurosporine-induced hyperdifferentiated B16F10 (sB16F10) cells expressed calreticulin on their surface and were phagocytosed efficiently. Furthermore, the inoculation of mice with sB16F10 cells induced immune responses against tumor-derived antigens. Despite the immunogenicity of sB16F10 cells, they activated the PD-1/PD-L1 immune checkpoint system and strongly resisted T cell-mediated tumor destruction. However, in vivo treatment with immune checkpoint inhibitors successfully eliminated the tumor. Thus, hyperdifferentiated melanoma cells have conflicting immunological properties – enhanced immunogenicity and immune evasion. Inhibiting the ability of PSMCs to evade T cell-mediated elimination might lead to complete melanoma eradication. |
| format | Article |
| id | doaj-art-da4edba508444df6a6013d784c26b82b |
| institution | Kabale University |
| issn | 2162-402X |
| language | English |
| publishDate | 2025-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | OncoImmunology |
| spelling | doaj-art-da4edba508444df6a6013d784c26b82b2024-12-09T05:02:37ZengTaylor & Francis GroupOncoImmunology2162-402X2025-12-0114110.1080/2162402X.2024.2437211Hyperdifferentiated murine melanoma cells promote adaptive anti-tumor immunity but activate the immune checkpoint systemYukie Ando0Yutaka Horiuchi1Sara Hatazawa2Momo Mataki3Akihiro Nakamura4Takashi Murakami5Department of Microbiology, Saitama Medical University, Moroyama-cho, Saitama,JapanDepartment of Microbiology, Saitama Medical University, Moroyama-cho, Saitama,JapanDepartment of Microbiology, Saitama Medical University, Moroyama-cho, Saitama,JapanDepartment of Microbiology, Saitama Medical University, Moroyama-cho, Saitama,JapanDepartment of Microbiology, Saitama Medical University, Moroyama-cho, Saitama,JapanDepartment of Microbiology, Saitama Medical University, Moroyama-cho, Saitama,JapanAccumulating evidence suggests that phenotype switching of cancer cells is essential for therapeutic resistance. However, the immunological characteristics of drug-induced phenotype-switching melanoma cells (PSMCs) are unknown. We investigated PSMC elimination by host immunity using hyperdifferentiated melanoma model cells derived from murine B16F10 melanoma cells. Exposure of B16F10 cells to staurosporine induced a hyperdifferentiated phenotype associated with transient drug tolerance. Staurosporine-induced hyperdifferentiated B16F10 (sB16F10) cells expressed calreticulin on their surface and were phagocytosed efficiently. Furthermore, the inoculation of mice with sB16F10 cells induced immune responses against tumor-derived antigens. Despite the immunogenicity of sB16F10 cells, they activated the PD-1/PD-L1 immune checkpoint system and strongly resisted T cell-mediated tumor destruction. However, in vivo treatment with immune checkpoint inhibitors successfully eliminated the tumor. Thus, hyperdifferentiated melanoma cells have conflicting immunological properties – enhanced immunogenicity and immune evasion. Inhibiting the ability of PSMCs to evade T cell-mediated elimination might lead to complete melanoma eradication.https://www.tandfonline.com/doi/10.1080/2162402X.2024.2437211Anti-tumor immunityimmune checkpoint inhibitorsmalignant melanomaphenotype switching |
| spellingShingle | Yukie Ando Yutaka Horiuchi Sara Hatazawa Momo Mataki Akihiro Nakamura Takashi Murakami Hyperdifferentiated murine melanoma cells promote adaptive anti-tumor immunity but activate the immune checkpoint system OncoImmunology Anti-tumor immunity immune checkpoint inhibitors malignant melanoma phenotype switching |
| title | Hyperdifferentiated murine melanoma cells promote adaptive anti-tumor immunity but activate the immune checkpoint system |
| title_full | Hyperdifferentiated murine melanoma cells promote adaptive anti-tumor immunity but activate the immune checkpoint system |
| title_fullStr | Hyperdifferentiated murine melanoma cells promote adaptive anti-tumor immunity but activate the immune checkpoint system |
| title_full_unstemmed | Hyperdifferentiated murine melanoma cells promote adaptive anti-tumor immunity but activate the immune checkpoint system |
| title_short | Hyperdifferentiated murine melanoma cells promote adaptive anti-tumor immunity but activate the immune checkpoint system |
| title_sort | hyperdifferentiated murine melanoma cells promote adaptive anti tumor immunity but activate the immune checkpoint system |
| topic | Anti-tumor immunity immune checkpoint inhibitors malignant melanoma phenotype switching |
| url | https://www.tandfonline.com/doi/10.1080/2162402X.2024.2437211 |
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