Carbon ion radiotherapy combined with immunotherapy: synergistic anti-tumor efficacy and preliminary investigation of ferroptosis.

Huang, Qingting; Hu, Jiyi; Chen, Li; Lin, Wanzun; Yang, Jing; Hu, Weixu; Gao, Jing; Zhang, Haojiong; Lu, Jiade Jay; Kong, Lin

Huang, Qingting; Hu, Jiyi; Chen, Li; Lin, Wanzun; Yang, Jing; Hu, Weixu; Gao, Jing; Zhang, Haojiong; Lu, Jiade Jay; Kong, Lin.

Afiliación

Huang Q; Department of Radiation Oncology, Shanghai Proton and Heavy Ion Center, Shanghai, 201321, China.
Hu J; Department of Radiation Oncology, Shanghai Proton and Heavy Ion Center, Fudan University Cancer Hospital, Shanghai, 201321, China.
Chen L; Shanghai Key Laboratory of Radiation Oncology (20dz2261000), Shanghai, 201321, China.
Lin W; Shanghai Engineering Research Center of Proton and Heavy Ion Radiation Therapy, Shanghai, 201321, China.
Yang J; Department of Radiation Oncology, Shanghai Proton and Heavy Ion Center, Fudan University Cancer Hospital, Shanghai, 201321, China.
Hu W; Shanghai Key Laboratory of Radiation Oncology (20dz2261000), Shanghai, 201321, China.
Gao J; Shanghai Engineering Research Center of Proton and Heavy Ion Radiation Therapy, Shanghai, 201321, China.
Zhang H; Department of Radiation Oncology, Shanghai Proton and Heavy Ion Center, Shanghai, 201321, China.
Lu JJ; Department of Radiation Oncology, Shanghai Proton and Heavy Ion Center, Fudan University Cancer Hospital, Shanghai, 201321, China.
Kong L; Shanghai Key Laboratory of Radiation Oncology (20dz2261000), Shanghai, 201321, China.

Cancer Immunol Immunother ; 72(12): 4077-4088, 2023 Dec.

Article en En | MEDLINE | ID: mdl-37777634

RESUMEN

Carbon ion radiotherapy (CIRT) may yield satisfactory clinical outcomes for patients who are resistant to radiotherapy. However, the therapeutic impact of carbon ions is still limited in certain recurring or refractory tumors. Therefore, we aimed to evaluate the synergistic anti-tumor effects of immune checkpoint inhibitors (ICIs) in combination with CIRT. We then explored the involvement of ferroptosis in a preliminary investigation. A tumor-bearing mouse model was established, and mice were inoculated subcutaneously with B16-OVA cells into the flanks of both hind legs. Mice were assigned to four groups to receive CIRT, ICIs, or combined treatment. Thereafter, we conducted transcriptome sequencing (RNA-seq), bioinformatics analysis, and various immune-related experiments on the available tumor tissues to investigate differences in the synergistic anticancer effects and potential mechanisms across the groups. The combination therapies significantly improved the survival of mice and inhibited tumor growth, both at local and distant sites. Based on bioinformatics and RNA-seq data, immune-related pathways and genes, immune cell infiltration, and the production of cytokines and chemokines were the most enhanced in the combined treatment group compared to other groups. Finally, we identified a potential role for ferroptosis in the development of local anti-tumor synergy during CIRT combination treatment. In conclusion, this study showed that CIRT and ICIs can enhance the anti-tumor immune effects. We also proposed that ferroptosis may induce anti-tumor effects in CIRT combination therapy, offering a unique perspective on its ability to enhance immunotherapy responses.

Asunto(s)

Ferroptosis; Radioterapia de Iones Pesados; Humanos; Recurrencia Local de Neoplasia/patología; Terapia Combinada; Inmunoterapia

Palabras clave

Anti-tumor efficacy; Carbon ion radiotherapy; Ferroptosis; Immunotherapy

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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Radioterapia de Iones Pesados / Ferroptosis Límite: Humans Idioma: En Revista: Cancer Immunol Immunother Asunto de la revista: ALERGIA E IMUNOLOGIA / NEOPLASIAS / TERAPEUTICA Año: 2023 Tipo del documento: Article País de afiliación: China Pais de publicación: Alemania

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