Zhu Yankun, Meng Mingyao, Hou Zongliu, Wang Wenju, Li Lin, Guan Aoran, Wang Ruotian, Tang Weiwei, Yang Fang, Zhao Yiyi, Gao Hui, Xie Hui, Li Ruhong, Tan Jing
Department of General Surgery, Yan'an Hospital Affiliated to Kunming Medical University, Kunming, China.
Key Laboratory of Tumor Immunological Prevention and Treatment in Yunnan Province, Yan'an Hospital Affiliated to Kunming Medical University, Kunming, China.
Front Oncol. 2023 Jan 16;13:1122669. doi: 10.3389/fonc.2023.1122669. eCollection 2023.
Expansion and activation of cytotoxic T lymphocytes (CTLs) represents a promising immunotherapeutic strategy, and CTLs can be primed by dendritic cells (DCs) loaded with tumor-associated antigens (TAAs) transformed by recombinant adeno-associated virus (rAAV). This study aimed to explore the impact of rAAV-DC-induced CTLs on prognosis of CRC and to explore factors associated with prognosis.
This prospective observational study included patients operated for CRC at Yan'an Hospital Affiliated to Kunming Medical University between 2016 and 2019. The primary outcome was progression-free survival (PFS), secondary outcomes were overall survival (OS) and adverse events. Totally 49 cases were included, with 29 and 20 administered rAAV-DC-induced CTL and chemotherapy, respectively.
After 37-69 months of follow-up (median, 54 months), OS (P=0.0596) and PFS (P=0.0788) were comparable between two groups. Mild fever occurred in 2 (6.9%) patients administered CTL infusion. All the chemotherapy group experienced mild-to-moderate adverse effects, including vasculitis (n=20, 100%), vomiting (n=5, 25%), nausea (n=17, 85%) and fatigue (n=17, 85%).
Lymphatic metastasis (hazard ratio [HR]=4.498, 95% confidence interval [CI]: 1.290-15.676; P=0.018) and lower HLA-I expression (HR=0.294, 95%CI: 0.089-0.965; P=0.044) were associated with poor OS in the CTL group. CTLs induced by rAAV-DCs might achieve comparable effectiveness in CRC patients compare to chemotherapy, cases with high tumor-associated HLA-I expression and no lymphatic metastasis were more likely to benefit from CTLs.
细胞毒性T淋巴细胞（CTL）的扩增和激活是一种很有前景的免疫治疗策略，并且CTL可由负载有经重组腺相关病毒（rAAV）转化的肿瘤相关抗原（TAA）的树突状细胞（DC）启动。本研究旨在探讨rAAV-DC诱导的CTL对结直肠癌预后的影响，并探索与预后相关的因素。
这项前瞻性观察性研究纳入了2016年至2019年期间在昆明医科大学附属延安医院接受结直肠癌手术的患者。主要结局为无进展生存期（PFS），次要结局为总生存期（OS）和不良事件。共纳入49例患者，其中29例接受rAAV-DC诱导的CTL治疗，20例接受化疗。
经过37 - 69个月的随访（中位时间为54个月），两组的OS（P = 0.0596）和PFS（P = 0.0788）相当。接受CTL输注的2例（6.9%）患者出现轻度发热。所有化疗组均经历了轻度至中度的不良反应，包括血管炎（n = 20，100%）、呕吐（n = 5，25%）、恶心（n = 17，85%）和疲劳（n = 17，85%）。
在CTL组中，淋巴结转移（风险比[HR] = 4.498，95%置信区间[CI]：1.290 - 15.676；P = 0.018）和较低的HLA-I表达（HR = 0.294, 95%CI：0.089 - 0.965；P = 0.044）与较差的OS相关。与化疗相比，rAAV-DC诱导的CTL在结直肠癌患者中可能取得相当的疗效，肿瘤相关HLA-I表达高且无淋巴结转移的病例更可能从CTL治疗中获益。
