Chitooligosaccharides Improve the Efficacy of Checkpoint Inhibitors in a Mouse Model of Lung Cancer
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 deacety...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-05-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/14/5/1046 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Astrid Zedlitz Johansen |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T03:06:38Z |
| format | Article |
| id | doaj.art-78186d8268bd442d8ea8f1b9fe7ac71e |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-10T03:06:38Z |
| publishDate | 2022-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-78186d8268bd442d8ea8f1b9fe7ac71e2023-11-23T12:38:43ZengMDPI AGPharmaceutics1999-49232022-05-01145104610.3390/pharmaceutics14051046Chitooligosaccharides Improve the Efficacy of Checkpoint Inhibitors in a Mouse Model of Lung CancerAstrid Zedlitz Johansen0Marco Carretta1Marie-Louise Thorseth2Shawez Khan3Klaire Yixin Fjæstad4Christian Beltoft Brøchner5Hannes Linder6Christina Ankjærgaard7Marco Donia8Inna Chen9Dorte Lisbet Nielsen10Claus Preibisch Behrens11Daniel Hargbøl Madsen12National Center for Cancer Immune Therapy, Department of Oncology, Copenhagen University Hospital—Herlev and Gentofte, 2730 Herlev, DenmarkNational Center for Cancer Immune Therapy, Department of Oncology, Copenhagen University Hospital—Herlev and Gentofte, 2730 Herlev, DenmarkNational Center for Cancer Immune Therapy, Department of Oncology, Copenhagen University Hospital—Herlev and Gentofte, 2730 Herlev, DenmarkNational Center for Cancer Immune Therapy, Department of Oncology, Copenhagen University Hospital—Herlev and Gentofte, 2730 Herlev, DenmarkNational Center for Cancer Immune Therapy, Department of Oncology, Copenhagen University Hospital—Herlev and Gentofte, 2730 Herlev, DenmarkDepartment of Pathology, Centre of Diagnostic Investigations, Copenhagen University Hospital—Rigshospitalet, 2100 Copenhagen, DenmarkNational Center for Cancer Immune Therapy, Department of Oncology, Copenhagen University Hospital—Herlev and Gentofte, 2730 Herlev, DenmarkDepartment of Health Technology, Technical University of Denmark, 4000 Roskilde, DenmarkNational Center for Cancer Immune Therapy, Department of Oncology, Copenhagen University Hospital—Herlev and Gentofte, 2730 Herlev, DenmarkDepartment of Oncology, Copenhagen University Hospital—Herlev and Gentofte, 2730 Herlev, DenmarkDepartment of Oncology, Copenhagen University Hospital—Herlev and Gentofte, 2730 Herlev, DenmarkDepartment of Health Technology, Technical University of Denmark, 4000 Roskilde, DenmarkNational Center for Cancer Immune Therapy, Department of Oncology, Copenhagen University Hospital—Herlev and Gentofte, 2730 Herlev, DenmarkYKL-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.https://www.mdpi.com/1999-4923/14/5/1046checkpoint inhibitorschitinchitooligosaccharidesimmunotherapylung cancerradiotherapy |
| spellingShingle | 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 Chitooligosaccharides Improve the Efficacy of Checkpoint Inhibitors in a Mouse Model of Lung Cancer Pharmaceutics checkpoint inhibitors chitin chitooligosaccharides immunotherapy lung cancer radiotherapy |
| title | Chitooligosaccharides Improve the Efficacy of Checkpoint Inhibitors in a Mouse Model of Lung Cancer |
| title_full | Chitooligosaccharides Improve the Efficacy of Checkpoint Inhibitors in a Mouse Model of Lung Cancer |
| title_fullStr | Chitooligosaccharides Improve the Efficacy of Checkpoint Inhibitors in a Mouse Model of Lung Cancer |
| title_full_unstemmed | Chitooligosaccharides Improve the Efficacy of Checkpoint Inhibitors in a Mouse Model of Lung Cancer |
| title_short | Chitooligosaccharides Improve the Efficacy of Checkpoint Inhibitors in a Mouse Model of Lung Cancer |
| title_sort | chitooligosaccharides improve the efficacy of checkpoint inhibitors in a mouse model of lung cancer |
| topic | checkpoint inhibitors chitin chitooligosaccharides immunotherapy lung cancer radiotherapy |
| url | https://www.mdpi.com/1999-4923/14/5/1046 |
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