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Article

Immunogenic Cell Death by the Novel Topoisomerase I Inhibitor TLC388 Enhances the Therapeutic Efficacy of Radiotherapy

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Department of Biomedical Imaging and Radiological Science, China Medical University, Taichung 40402, Taiwan
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Translation Research Core, China Medical University Hospital, China Medical University, Taichung 40402, Taiwan
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Lab of Precision Medicine, Feng-Yuan Hospital, Ministry of Health and Welfare, Taichung 42055, Taiwan
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Cancer Center, China Medical University Hospital, China Medical University, Taichung 40402, Taiwan
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Department of Colorectal Surgery, China Medical University Hospital, China Medical University, Taichung 40402, Taiwan
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School of Chinese Medicine & Graduate Institute of Chinese Medicine, China Medical University, Taichung 40402, Taiwan
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Department of Pathology, Asia University Hospital, Asia University, Taichung 41354, Taiwan
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Graduate Institute of Biomedical Science, China Medical University, Taichung 40402, Taiwan
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Department of Surgery, School of Medicine, China Medical University, Taichung 40402, Taiwan
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Department of Colorectal Surgery, China Medical University HsinChu Hospital, China Medical University, HsinChu 302, Taiwan
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Department of Radiotherapy, School of Medicine, China Medical University, Taichung 40402, Taiwan
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Authors to whom correspondence should be addressed.
Academic Editors: Meritxell Arenas and Pierfrancesco Franco
Cancers 2021, 13(6), 1218; https://doi.org/10.3390/cancers13061218
Received: 14 January 2021 / Revised: 7 March 2021 / Accepted: 8 March 2021 / Published: 11 March 2021
(This article belongs to the Special Issue Cancer Radiotherapy)
This study aims to evaluate the induction of immunogenic cell death (ICD) for anticancer immunity by the novel topoisomerase I inhibitor lipotecan. These results show that lipotecan can remarkably elicit ICD and increase tumor immunogenicity, which promotes the therapeutic efficacy of radiotherapy compared to conventional chemoradiotherapy in vivo. These results provide potential therapeutic strategies to improve the efficacy of chemoradiotherapy in colorectal cancer (CRC), which may increase the local control rate and decrease tumor relapse in locally advanced rectal cancer (LARC) patients who receive preoperative chemoradiotherapy.
Rectal cancer accounts for 30–40% of colorectal cancer (CRC) and is the most common cancer-related death worldwide. The preoperative neoadjuvant chemoradiotherapy (neoCRT) regimen is the main therapeutic strategy for patients with locally advanced rectal cancer (LARC) to control tumor growth and reduce distant metastasis. However, 30–40% of patients achieve a partial response to neoCRT and suffer from unnecessary drug toxicity side effects and a risk of distant metastasis. In our study, we found that the novel topoisomerase I inhibitor lipotecan (TLC388) can elicit immunogenic cell death (ICD) to release damage-associated molecular patterns (DAMPs), including HMGB1, ANXA1, and CRT exposure. Lipotecan thereby increases cancer immunogenicity and triggers an antitumor immune response to attract immune cell infiltration within the tumor microenvironment (TME) in vitro and in vivo. Taken together, these results show that lipotecan can remodel the tumor microenvironment to provoke anticancer immune responses, which can provide potential clinical benefits to the therapeutic efficacy of neoCRT in LARC patients. View Full-Text
Keywords: locally advanced rectal cancer; neoadjuvant chemoradiotherapy; topoisomerase I inhibitor; lipotecan; anticancer immunity locally advanced rectal cancer; neoadjuvant chemoradiotherapy; topoisomerase I inhibitor; lipotecan; anticancer immunity
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MDPI and ACS Style

Huang, K.C.-Y.; Chiang, S.-F.; Yang, P.-C.; Ke, T.-W.; Chen, T.-W.; Hu, C.-H.; Huang, Y.-W.; Chang, H.-Y.; Chen, W.T.-L.; Chao, K.S.C. Immunogenic Cell Death by the Novel Topoisomerase I Inhibitor TLC388 Enhances the Therapeutic Efficacy of Radiotherapy. Cancers 2021, 13, 1218. https://doi.org/10.3390/cancers13061218

AMA Style

Huang KC-Y, Chiang S-F, Yang P-C, Ke T-W, Chen T-W, Hu C-H, Huang Y-W, Chang H-Y, Chen WT-L, Chao KSC. Immunogenic Cell Death by the Novel Topoisomerase I Inhibitor TLC388 Enhances the Therapeutic Efficacy of Radiotherapy. Cancers. 2021; 13(6):1218. https://doi.org/10.3390/cancers13061218

Chicago/Turabian Style

Huang, Kevin C.-Y., Shu-Fen Chiang, Pei-Chen Yang, Tao-Wei Ke, Tsung-Wei Chen, Ching-Han Hu, Yi-Wen Huang, Hsin-Yu Chang, William T.-L. Chen, and K. S.C. Chao 2021. "Immunogenic Cell Death by the Novel Topoisomerase I Inhibitor TLC388 Enhances the Therapeutic Efficacy of Radiotherapy" Cancers 13, no. 6: 1218. https://doi.org/10.3390/cancers13061218

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