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Article

Chitooligosaccharides Improve the Efficacy of Checkpoint Inhibitors in a Mouse Model of Lung Cancer

1
National Center for Cancer Immune Therapy, Department of Oncology, Copenhagen University Hospital—Herlev and Gentofte, 2730 Herlev, Denmark
2
Department of Pathology, Centre of Diagnostic Investigations, Copenhagen University Hospital—Rigshospitalet, 2100 Copenhagen, Denmark
3
Department of Health Technology, Technical University of Denmark, 4000 Roskilde, Denmark
4
Department of Oncology, Copenhagen University Hospital—Herlev and Gentofte, 2730 Herlev, Denmark
5
Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark
6
Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark
*
Author to whom correspondence should be addressed.
Academic Editor: Fabiana Quaglia
Pharmaceutics 2022, 14(5), 1046; https://doi.org/10.3390/pharmaceutics14051046
Received: 31 March 2022 / Revised: 6 May 2022 / Accepted: 9 May 2022 / Published: 12 May 2022
(This article belongs to the Special Issue Application of Chitosan and Hyaluronan in Medicine)
YKL-40 (also named chitinase 3 like-1 protein [CHI3L1]) is a secreted chitinase-like protein which is upregulated in cancers and suggested to have pro-tumorigenic activity. YKL-40 lacks enzymatic function, but it can bind carbohydrates such as chitin. Chitooligosaccharides (COS) derived from deacetylation and hydrolysis of chitin might be used for the blockade of YKL-40 function. Here, public single-cell RNA sequencing datasets were used to elucidate the cellular source of YKL-40 gene expression in human tumors. Fibroblasts and myeloid cells were the primary sources of YKL-40. Screening of YKL-40 gene expression in syngeneic mouse cancer models showed the highest expression in the Lewis lung carcinoma (LL2) model. LL2 was used to investigate COS monotherapy and combinations with immune checkpoint inhibitors (anti-PD-L1 and anti-CTLA-4) (ICIs) and radiotherapy (8 Gy × 3) (RT). COS tended to reduce plasma YKL-40 levels, but it did not affect tumor growth. LL2 showed minimal responses to ICIs, or to RT alone. Interestingly, ICIs combined with COS led to delayed tumor growth. RT also enhanced the efficacy of ICIs; however, the addition of COS did not further delay the tumor growth. COS may exert their anti-tumorigenic effects through the inhibition of YKL-40, but additional functions of COS should be investigated. View Full-Text
Keywords: checkpoint inhibitors; chitin; chitooligosaccharides; immunotherapy; lung cancer; radiotherapy; syngeneic mouse cancer models; YKL-40 checkpoint inhibitors; chitin; chitooligosaccharides; immunotherapy; lung cancer; radiotherapy; syngeneic mouse cancer models; YKL-40
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MDPI and ACS Style

Johansen, A.Z.; Carretta, M.; Thorseth, M.-L.; Khan, S.; Fjæstad, K.Y.; Brøchner, C.B.; Linder, H.; Ankjærgaard, C.; Donia, M.; Chen, I.; Nielsen, D.L.; Behrens, C.P.; Madsen, D.H. Chitooligosaccharides Improve the Efficacy of Checkpoint Inhibitors in a Mouse Model of Lung Cancer. Pharmaceutics 2022, 14, 1046. https://doi.org/10.3390/pharmaceutics14051046

AMA Style

Johansen AZ, Carretta M, Thorseth M-L, Khan S, Fjæstad KY, Brøchner CB, Linder H, Ankjærgaard C, Donia M, Chen I, Nielsen DL, Behrens CP, Madsen DH. Chitooligosaccharides Improve the Efficacy of Checkpoint Inhibitors in a Mouse Model of Lung Cancer. Pharmaceutics. 2022; 14(5):1046. https://doi.org/10.3390/pharmaceutics14051046

Chicago/Turabian Style

Johansen, Astrid Z., Marco Carretta, Marie-Louise Thorseth, Shawez Khan, Klaire Y. Fjæstad, Christian B. Brøchner, Hannes Linder, Christina Ankjærgaard, Marco Donia, Inna Chen, Dorte L. Nielsen, Claus P. Behrens, and Daniel H. Madsen. 2022. "Chitooligosaccharides Improve the Efficacy of Checkpoint Inhibitors in a Mouse Model of Lung Cancer" Pharmaceutics 14, no. 5: 1046. https://doi.org/10.3390/pharmaceutics14051046

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