Adoptive transfer of natural killer cells in combination with chemotherapy improves outcomes of patients with locally advanced colon carcinoma

Autor: Dongsheng Xu, Lingyu Li, Fujun Han, Chao Niu, Wei Li, Wei Han, Cheng Yao, Yizhuo Wang, Chang Wang, Min Li, Xu Yan, Jiuwei Cui, Huimin Tian, Dan Li, Haofan Jin, Xiaoying Zhang
Rok vydání: 2018
Předmět:
Cytotoxicity
Immunologic
Male
0301 basic medicine
Oncology
Cancer Research
medicine.medical_specialty
Adoptive cell transfer
Colorectal cancer
medicine.medical_treatment
Immunology
Ligands
Immunotherapy
Adoptive
Cohort Studies
Cell therapy
03 medical and health sciences
0302 clinical medicine
Cell Line
Tumor
Internal medicine
medicine
Humans
Immunology and Allergy
Progression-free survival
Adverse effect
Genetics (clinical)
Neoplasm Staging
Transplantation
Chemotherapy
business.industry
Cell Differentiation
Cell Biology
Middle Aged
Prognosis
medicine.disease
Progression-Free Survival
Oxaliplatin
Killer Cells
Natural
Treatment Outcome
030104 developmental biology
030220 oncology & carcinogenesis
Colonic Neoplasms
Neoplastic Stem Cells
Female
Neoplasm Recurrence
Local
Stem cell
business
medicine.drug
Zdroj: Cytotherapy. 20:134-148
ISSN: 1465-3249
DOI: 10.1016/j.jcyt.2017.09.009
Popis: Background Despite the availability of multiple treatment strategies, patients with advanced colon carcinoma (CC) have poor prognoses. The aim of this study was to evaluate the efficacy and safety of natural killer (NK) cell therapy in combination with chemotherapy in patients with locally advanced CC. Methods We assessed the cytotoxicity of NK cells to CC cells (CCs) and CC stem cells (CSCs) pre-treated with 5-fluorouracil or oxaliplatin in vitro. Then, an open-label cohort study was conducted with locally advanced CC patients who had received radical resection. Patients received either NK cell therapy combined with chemotherapy (NK cell group, 27 patients) or pure chemotherapy (control group, 33 patients). Progression-free survival (PFS), overall survival (OS) and adverse effects were investigated. Results Chemotherapy sensitized CCs and CSCs to NK cell cytotoxicity through regulation of NK cell–activating/inhibitory receptor ligands. Poorly differentiated CCs were more susceptible to NK cells than well-differentiated ones. In the cohort study, the 5-year PFS and OS rates in the NK cell group were significantly higher than those in the control group (51.1% versus 35%, P = 0.044; 72.5% versus 51.6%, P = 0.037, respectively). Among patients with poorly differentiated carcinomas and low expression of human leukocyte antigen (HLA)-1, the median PFS in the NK cell group versus the control group was 23.5 versus 12.1 months (P = 0.0475) and 33.1 versus 18.5 months (P = 0.045), respectively. No significant adverse reactions were reported. Conclusion NK cell therapy in combination with chemotherapy in locally advanced CC prevented recurrence and prolonged survival with acceptable adverse effects, especially for poorly differentiated carcinomas.
Databáze: OpenAIRE
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