在胃癌异种移植模型中,通过向肿瘤内部注射养护性NK细胞与卡比替宁进行化疗免疫细胞疗法。
Chemo-immune cell therapy by intratumoral injection of adoptive NK cells with capecitabine in gastric cancer xenograft model.
发表日期:2023
作者:
Zeinab Ghazvinian, Shahrokh Abdolahi, Mohammad Ahmadvand, Amir Hossein Emami, Samad Muhammadnejad, Hamid Asadzadeh Aghdaei, Jafar Ai, Mohammad Reza Zali, Iman Seyhoun, Javad Verdi, Kaveh Baghaei
来源:
Stem Cell Research & Therapy
摘要:
胃癌是最常见的恶性肿瘤之一,也是全球第五大癌症相关死因。而自然杀伤(NK)细胞在肿瘤消除中起到关键作用,因此,采用NK细胞养护治疗已成为肿瘤细胞治疗中一种有前景的方法。因此,本研究调查了MKN-45源性异种移植胃癌模型中的化疗免疫细胞治疗。动物分为三组,分别接受以下治疗:激活的NK细胞、卡培他滨,卡培他滨与激活的NK细胞的联合治疗,以及一个作为对照组。研究结束时评估了肿瘤样本的形态测量特性。通过hCD56的免疫组织化学(IHC)评估了NK细胞的浸润情况。通过苏木精和伊红(H&E)染色评估了有丝分裂计数和治疗反应。通过Ki67和caspase 3的IHC评估来确定增殖与凋亡的比率。结果表明,NK细胞治疗可以在病理评估中有效降低有丝分裂计数,但肿瘤并未完全消除。与卡培他滨的持续化疗(MC)联合使用时,NK细胞治疗在肿瘤形态测量特性方面与对照组相比存在显著差异。增殖与凋亡比率也与病理数据一致。尽管NK细胞治疗在体内可以有效降低有丝分裂计数,但所得结果表明其效力较MC低,尽管在体外激活时效果较好。为提高NK细胞治疗的有效性,应考虑肿瘤微环境的抑制特征和抑制性免疫检查点的阻断。©2023作者
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 in vivo, the obtained findings indicated lesser potency than MC despite ex vivo activation. In order to enhance NK cell therapy effectiveness, suppressive features of the tumor microenvironment and inhibitory immune checkpoints blockade should be considered.© 2023 The Author(s).