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Theranostics 2023; 13(1):40-58. doi:10.7150/thno.77233 This issue Cite

Review

Nanoparticles augment the therapeutic window of RT and immunotherapy for treating cancers: pivotal role of autophagy

Yuan-Hua Wu^1*, Rong-Jane Chen^2*, Hui-Wen Chiu^3,4,5, Li-Xing Yang⁶, Yung-Li Wang³, Yu-Ying Chen⁷, Ya-Ling Yeh⁷, Mei-Yi Liao^8✉, Ying-Jan Wang^7,9✉

1. Department of Radiation Oncology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan.
2. Department of Food Safety/Hygiene and Risk Management, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan.
3. Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan.
4. Department of Medical Research, Shuang Ho Hospital, Taipei Medical University, New Taipei City 234, Taiwan.
5. TMU Research Center of Urology and Kidney, Taipei Medical University, Taipei 110, Taiwan.
6. Institute of Oral Medicine and Department of Stomatology, College of Medicine, National Cheng Kung University Hospital, National Cheng Kung University, Tainan 701, Taiwan.
7. Department of Environmental and Occupational Health, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan.
8. Department of Applied Chemistry, National Pingtung University, Pingtung 900, Taiwan.
9. Department of Medical Research, China Medical University Hospital, China Medical University, Taichung 404, Taiwan.
*These authors contributed equally to this work.

✉ Corresponding authors: myliaonptu.edu.tw (M.-Y.L.); yjwangncku.edu.tw (Y.-J.W.); +886-6-235-3535 (ext. 5804) (Y.-J.W.).

Abstract

Immunotherapies are now emerging as an efficient anticancer therapeutic strategy. Cancer immunotherapy utilizes the host's immune system to fight against cancer cells and has gained increasing interest due to its durable efficacy and low toxicity compared to traditional antitumor treatments, such as chemotherapy and radiotherapy (RT). Although the combination of RT and immunotherapy has drawn extensive attention in the clinical setting, the overall response rates are still low. Therefore, strategies for further improvement are urgently needed. Nanotechnology has been used in cancer immunotherapy and RT to target not only cancer cells but also the tumor microenvironment (TME), thereby helping to generate a long-term immune response. Nanomaterials can be an effective delivery system and a strong autophagy inducer, with the ability to elevate autophagy to very high levels. Interestingly, autophagy could play a critical role in optimal immune function, mediating cell-extrinsic homeostatic effects through the regulation of danger signaling in neoplastic cells under immunogenic chemotherapy and/or RT. In this review, we summarize the preclinical and clinical development of the combination of immunotherapy and RT in cancer therapy and highlight the latest progress in nanotechnology for augmenting the anticancer effects of immunotherapy and RT. The underlying mechanisms of nanomaterial-triggered autophagy in tumor cells and the TME are discussed in depth. Finally, we suggest the implications of these three strategies combined together to achieve the goal of maximizing the therapeutic advantages of cancer therapy and show recent advances in biomarkers for tumor response in the evaluation of those therapies.

Keywords: radiotherapy, immunotherapy, nanomaterials, autophagy, tumor microenvironment

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