Ghazvinian Zeinab, Abdolahi Shahrokh, Ahmadvand Mohammad, Emami Amir Hossein, Muhammadnejad Samad, Asadzadeh Aghdaei Hamid, Ai Jafar, Zali Mohammad Reza, Seyhoun Iman, Verdi Javad, Baghaei Kaveh
Department of Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Hematology-Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, Tehran, Iran.
Bioimpacts. 2023;13(5):383-392. doi: 10.34172/bi.2022.26386. Epub 2022 Sep 18.
Gastric cancer is one of the most commonly known malignancies and is the fifth cancer-related death globally. Whereas natural killer (NK) cells play a critical role in tumor elimination; therefore, adoptive NK cell therapy has become a promising approach in cancer cytotherapy. Hence, this study investigated the chemo-immune cell therapy in MKN-45 derived xenograft gastric cancer model.
Three groups of animals have received the following treatments separately: activated NK cells, capecitabine, the combination of capecitabine and activated NK cells, and one was considered as the control group. Morphometric properties of tumor samples were evaluated at the end of the study. NK cells infiltration was evaluated by immunohistochemistry (IHC) of hCD56. Mitotic count and treatment response was assessed by hematoxylin and eosin (H&E) staining. The proliferation ratio to apoptosis was determined by IHC assessment of Ki67 and caspase 3.
The results indicated that the NK cell therapy could effectively decrease the mitotic count in pathology assessment, but the tumor was not completely eradicated. In combination with metronomic chemotherapy (MC) of capecitabine, NK cell therapy demonstrated a significant difference in tumor morphometric properties compared to the control group. The proliferation ratio to apoptosis was also in line with pathology data.
Although NK cell therapy could effectively decrease the mitotic count , the obtained findings indicated lesser potency than MC despite activation. In order to enhance NK cell therapy effectiveness, suppressive features of the tumor microenvironment and inhibitory immune checkpoints blockade should be considered.
胃癌是最常见的恶性肿瘤之一，是全球第五大致癌相关死亡原因。自然杀伤（NK）细胞在肿瘤清除中起关键作用；因此，过继性NK细胞疗法已成为癌症细胞治疗中一种有前景的方法。因此，本研究在MKN - 45衍生的异种移植胃癌模型中研究了化学免疫细胞疗法。
三组动物分别接受以下治疗：活化的NK细胞、卡培他滨、卡培他滨与活化NK细胞的联合治疗，另一组作为对照组。在研究结束时评估肿瘤样本的形态学特性。通过hCD56的免疫组织化学（IHC）评估NK细胞浸润情况。通过苏木精和伊红（H&E）染色评估有丝分裂计数和治疗反应。通过对Ki67和半胱天冬酶3的IHC评估确定增殖与凋亡的比率。
结果表明，NK细胞疗法在病理学评估中可有效降低有丝分裂计数，但肿瘤未被完全根除。与卡培他滨的节拍化疗（MC）联合使用时，NK细胞疗法与对照组相比，在肿瘤形态学特性方面显示出显著差异。增殖与凋亡的比率也与病理学数据一致。
尽管NK细胞疗法可有效降低有丝分裂计数，但所得结果表明，尽管已活化，其效力仍低于MC。为提高NK细胞疗法的有效性，应考虑肿瘤微环境的抑制特性和抑制性免疫检查点阻断。
