Purpose:The main objective of this research was directed to evaluate the therapeutic effect of paclitaxel and nivolumab on cancer stem cells (CSCs) of experimentally generated hamster buccal pouch (HBP) carcinoma. Methods: 50 hamsters were grouped into five groups. GI: animals left untreated. GII: animals were painted with 7, 12-dimethylbenz (a) anthracene (DMBA) thrice a week. GIII: following DMBA application, animals injected intraperitoneally (IP) with nivolumab on days 7, 10 and 13. GIV: animals were treated with paclitaxel (IP), twice a week and metformin (IP), thrice a week. GV: animals were receiving a combination of nivolumab, paclitaxel and metformin.Following euthanization, right pouches were surgically excised, bisected with one section fixed and processed for H&E and immunohistochemical (IHC) examinations, and other section of the fresh tissue was used for evaluation by flow cytometric (FCM). Results: Gross observation histopathological, and IHC changes were recorded. By FCM, CD44+/CD24-and CD44+/CD24+ were detected. The results indicated that the CD44+/CD24-cells percentage in GI,
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