Prebiotics Modulate Gut Microbiota-mediated T-cell Immunity to Enhance the Inhibitory Effect of Sintilimab in Lewis Lung Adenocarcinoma Model Mice


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Abstract

Background: Sintilimab (Sin) helps the body to restore the anti-tumor response of T lymphocytes. However, in clinical use, the treatment process is more complicated due to adverse effects and different dosing regimens. It is not clear whether prebiotics (PREB) have a potentiating effect on Sin for lung adenocarcinoma, and this study intends to investigate the inhibitory effect, safety and possible mechanism of Sin combined with PREB on lung adenocarcinoma from animal experiments.

Methods: Lewis lung adenocarcinoma cells were inoculated into the right axilla of mice subcutaneously to prepare the Lewis lung cancer mouse model and treated in groups. The volume of transplanted tumors was measured, the histopathology of the liver and kidney of mice was observed by H&E staining, the levels of ALT, AST, UREA, CREA, WBC, RBC, and HGB in blood were analyzed biochemically; the ratio of T-cell subpopulations in blood, spleen, and bone marrow was detected by flow cytometry, the expression of PD-L1 in tumor tissue was detected by immunofluorescence staining, and 16S rRNA to analyze the diversity of fecal flora.

Results: Sin inhibited tumor growth and regulated immune cell homeostasis in lung adenocarcinoma mice, but liver and kidney histopathology showed different degrees of damage after Sin treatment, while the addition of PREB reduced liver and kidney damage in lung adenocarcinoma mice and promoted Sin's regulation of immune cells. In addition, the beneficial effects of Sin were associated with changes in intestinal flora diversity.

Conclusion: The mechanism by which Sintilimab combined with prebiotics inhibits tumor volume and regulates immune cell subpopulation balance in lung adenocarcinoma mice may be related to gut microbes.

About the authors

Qin Yan

Department of Oncology, Cancer Prevention and Treatment Institute of Chengdu, Chengdu Fifth People's Hospital (The Second Clinical Medical College，Affiliated Fifth People's Hospital of Chengdu University of Traditional Chinese Medicine)

Email: info@benthamscience.net

Shitong Su

Department of Head and Neck Oncology, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University,

Email: info@benthamscience.net

Gangyi Dai

Department of Oncology, Cancer Prevention and Treatment Institute of Chengdu, Chengdu Fifth People's Hospital (The Second Clinical Medical College，Affiliated Fifth People's Hospital of Chengdu University of Traditional Chinese Medicine)

Email: info@benthamscience.net

Lang He

Department of Oncology, Cancer Prevention and Treatment Institute of Chengdu, Chengdu Fifth People's Hospital (The Second Clinical Medical College，Affiliated Fifth People's Hospital of Chengdu University of Traditional Chinese Medicine)

Author for correspondence.
Email: info@benthamscience.net

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