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Evaluation of circulating innate lymphoid cells in the early pathogenesis of mouse colorectal carcinoma

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Abstract

Innate lymphoid cells (ILCs) have been shown to play essential roles in tumour immunity. Also, ILCs are involved in both homeostasis and inflammation. Evidence indicates that uncontrolled inflammatory response predisposes the intestine to colonic dysplasia and colorectal cancer (CRC). We investigated the frequency of three subsets of circulating ILCs in the early pathogenesis of colorectal carcinoma in the two distinct mouse models of colorectal cancer (CRC). We developed two mouse models representing the early pathogenic also reversible stages of CRC, including a chemically induced model, by administration of azoxymethane/dextran sulfate sodium (AOM/DSS), and an orthotopic mouse model, using the CT-26 cell line. Based on histopathological examinations, mice were divided into 3 groups including the dysplasia group (which consists of the chemically induced and the orthotopic induced), the chemically induced reparative change group, and a control group which was also considered in which mice were screened for stress originating from interventions and injections. Flow cytometry analysis was performed to evaluate the frequencies of ILC1, ILC2, and ILC3 in the peripheral blood of all studied mice. Altered composition of ILCs was observed in the peripheral blood of mice skewing toward ILC1s in the reparative change group compared to the control group (p value = 0.008); orthotopic-induced dysplasia and the chemically induced dysplasia groups did not differ significantly in terms of ILC subpopulations at the precancerous stages of colorectal dysplasia. A higher frequency of ILC1 in the chemically induced reparative change suggests a potentially anti-tumourigenic role participating in colorectal dysplasia.

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Acknowledgements

Words cannot express my gratitude to Dr. A. Ajami my professor and chair of the immunology department for their invaluable patience and feedback. Additionally, this endeavor would not have been possible without the generous support from the Mazandaran University of Medical science, which supported my research (grant number 2674). Also, I would like to extend my sincere thanks to Dr. Saeed Taghiloo and Dr. Ahmad Najafi who generously provided knowledge and expertise.

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Authors and Affiliations

  1. Department of Immunology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran

    Mohsen Keykhosravi, Seyed Mohammad Javadzadeh, Mohsen Tehrani, Hossein Asgarian-Omran, Hadi Hossein-Nattaj & Abolghasem Ajami

  2. Gastrointestinal Cancer Research Center, Mazandaran University of Medical Sciences, Sari, Iran

    Mohsen Tehrani & Hossein Asgarian-Omran

  3. Immunogenetic Research Center, Mazandaran University of Medical Sciences, Sari, Iran

    Hossein Asgarian-Omran

  4. Department of Pharmacology, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran

    Mohsen Rashidi

  5. Department of Pathology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran

    Laleh Vahedi-Larijani

  6. Molecular and Cell Biology Research Center, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran

    Abolghasem Ajami

  7. Antimicrobial Resistance Research Center, Communicable Diseases Institute, Mazandaran University of Medical Sciences, Sari, Iran

    Abolghasem Ajami

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  1. Mohsen Keykhosravi
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  8. Abolghasem Ajami
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Contributions

All authors contributed to the study. Abolghasem Ajami, Mohsen Tehrani, and Hossein Asgarian-Omran designed and conducted the research. Mohsen Rashidi managed the induction of a cancer model in mice. Laleh Vahedi-Larijani assessed the pathological status of samples. Seyed Mohammad Javadzadeh, Hadi Hossein-Nattaj, and Mohsen Keykhosravi carried out the assays, contributed to data collection and data analysis, and prepared the manuscript. All co-authors have read, informed, and approved the paper for publication in the journal of clinical comparative pathology.

Corresponding author

Correspondence to Abolghasem Ajami.

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Funding

This work was supported by the Gastrointestinal Cancer Research Center, Comprehensive Cancer Center, Imam Khomeini hospital of Sari, Mazandaran University of Medical Sciences (grant number: 2674) (grant recipient: Abolghasem Ajami).

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The authors declare that they have no conflict of interest.

Ethical approval

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving animals were under the ethical standards of the institution or practice at which the studies were conducted. All of the processes of maintenance and laboratory tests were approved by the ethic committee of Mazandaran University of Medical Sciences (IR.MAZUMS.REC.1397.2674).

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Keykhosravi, M., Javadzadeh, S.M., Tehrani, M. et al. Evaluation of circulating innate lymphoid cells in the early pathogenesis of mouse colorectal carcinoma. Comp Clin Pathol 32, 539–545 (2023). https://doi.org/10.1007/s00580-023-03462-5

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