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

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

Chitooligosaccharides Improve the Efficacy of Checkpoint Inhibitors in a Mouse Model of Lung Cancer. / Johansen, Astrid Zedlitz; Carretta, Marco; Thorseth, Marie Louise; Khan, Shawez; Fjæstad, Klaire Yixin; Brøchner, Christian Beltoft; Linder, Hannes; Ankjærgaard, Christina; Donia, Marco; Chen, Inna; Nielsen, Dorte Lisbet; Behrens, Claus Preibisch; Madsen, Daniel Hargbøl.

In: Pharmaceutics, Vol. 14, No. 5, 1046, 2022.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Johansen, AZ, Carretta, M, Thorseth, ML, Khan, S, Fjæstad, KY, Brøchner, CB, Linder, H, Ankjærgaard, C, Donia, M, Chen, I, Nielsen, DL, Behrens, CP & Madsen, DH 2022, 'Chitooligosaccharides Improve the Efficacy of Checkpoint Inhibitors in a Mouse Model of Lung Cancer', Pharmaceutics, vol. 14, no. 5, 1046. https://doi.org/10.3390/pharmaceutics14051046

APA

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. (2022). Chitooligosaccharides Improve the Efficacy of Checkpoint Inhibitors in a Mouse Model of Lung Cancer. Pharmaceutics, 14(5), [1046]. https://doi.org/10.3390/pharmaceutics14051046

Vancouver

Johansen AZ, Carretta M, Thorseth ML, Khan S, Fjæstad KY, Brøchner CB et al. 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

Author

Johansen, Astrid Zedlitz ; Carretta, Marco ; Thorseth, Marie Louise ; Khan, Shawez ; Fjæstad, Klaire Yixin ; Brøchner, Christian Beltoft ; Linder, Hannes ; Ankjærgaard, Christina ; Donia, Marco ; Chen, Inna ; Nielsen, Dorte Lisbet ; Behrens, Claus Preibisch ; Madsen, Daniel Hargbøl. / Chitooligosaccharides Improve the Efficacy of Checkpoint Inhibitors in a Mouse Model of Lung Cancer. In: Pharmaceutics. 2022 ; Vol. 14, No. 5.

Bibtex

@article{3246ae6cfe84447cbf49f891739647e0,
title = "Chitooligosaccharides Improve the Efficacy of Checkpoint Inhibitors in a Mouse Model of Lung Cancer",
abstract = "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.",
keywords = "checkpoint inhibitors, chitin, chitooligosaccharides, immunotherapy, lung cancer, radio-therapy, syngeneic mouse cancer models, YKL-40",
author = "Johansen, {Astrid Zedlitz} and Marco Carretta and Thorseth, {Marie Louise} and Shawez Khan and Fj{\ae}stad, {Klaire Yixin} and Br{\o}chner, {Christian Beltoft} and Hannes Linder and Christina Ankj{\ae}rgaard and Marco Donia and Inna Chen and Nielsen, {Dorte Lisbet} and Behrens, {Claus Preibisch} and Madsen, {Daniel Hargb{\o}l}",
note = "Publisher Copyright: {\textcopyright} 2022 by the authors. Licensee MDPI, Basel, Switzerland.",
year = "2022",
doi = "10.3390/pharmaceutics14051046",
language = "English",
volume = "14",
journal = "Pharmaceutics",
issn = "1999-4923",
publisher = "MDPI AG",
number = "5",

}

RIS

TY - JOUR

T1 - Chitooligosaccharides Improve the Efficacy of Checkpoint Inhibitors in a Mouse Model of Lung Cancer

AU - Johansen, Astrid Zedlitz

AU - Carretta, Marco

AU - Thorseth, Marie Louise

AU - Khan, Shawez

AU - Fjæstad, Klaire Yixin

AU - Brøchner, Christian Beltoft

AU - Linder, Hannes

AU - Ankjærgaard, Christina

AU - Donia, Marco

AU - Chen, Inna

AU - Nielsen, Dorte Lisbet

AU - Behrens, Claus Preibisch

AU - Madsen, Daniel Hargbøl

N1 - Publisher Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland.

PY - 2022

Y1 - 2022

N2 - 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.

AB - 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.

KW - checkpoint inhibitors

KW - chitin

KW - chitooligosaccharides

KW - immunotherapy

KW - lung cancer

KW - radio-therapy

KW - syngeneic mouse cancer models

KW - YKL-40

U2 - 10.3390/pharmaceutics14051046

DO - 10.3390/pharmaceutics14051046

M3 - Journal article

C2 - 35631632

AN - SCOPUS:85130352468

VL - 14

JO - Pharmaceutics

JF - Pharmaceutics

SN - 1999-4923

IS - 5

M1 - 1046

ER -

ID: 308042187