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

Astrid Zedlitz Johansen, Marco Carretta, Marie-Louise Thorseth, Shawez Khan, Klaire Yixin Fjæstad, Christian Beltoft Brøchner, Hannes Linder, Christina Ankjærgaard, Marco Donia, Inna Chen, Dorte Lisbet Nielsen, Claus Preibisch Behrens, Daniel Hargbøl Madsen*

*Corresponding author af dette arbejde

Abstrakt

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.

OriginalsprogEngelsk
Artikelnummer1046
TidsskriftPharmaceutics
Vol/bind14
Udgave nummer5
ISSN1999-4923
DOI
StatusUdgivet - 12 maj 2022

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