PO.CL05.07 · 临床研究
神经内分泌肿瘤中与肽受体放射性核素治疗相关的外周免疫特征
Peripheral immune signatures associated with peptide receptor radionuclide therapy in neuroendocrine tumors
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
背景：肽受体放射性核素治疗（PRRT）是一种针对生长抑素受体（SSTR）阳性神经内分泌肿瘤（NET）的内照射放疗。肿瘤微环境，特别是细胞毒性T淋巴细胞（CTL），是决定肿瘤行为、治疗反应和预后的关键因素，但NET通常表现为免疫细胞浸润稀疏的“冷”免疫微环境，这可能导致基于ICI疗法的疗效有限。外照射放疗可激活全身抗肿瘤免疫，偶尔可诱发远隔效应，即照射原发病灶可导致受照射部位和远处转移部位均缩小；然而，PRRT对全身免疫的影响却鲜有研究。我们假设PRRT可调节NET患者的全身免疫，并研究了循环细胞因子的变化。
方法：我们分析了横滨市立大学接受PRRT治疗的NET患者血清细胞因子水平的变化。收集来自9例患者的12对PRRT前后血清样本，并用36重细胞因子阵列进行分析。
结果：在9例患者中，7例正在接受首个PRRT疗程，2例接受第二个疗程（既往接受过四次给药的PRRT疗程并至少达到部分缓解、疾病控制≥1.5年后的再治疗）。原发部位为胰腺（n=6）、直肠（n=1）、肺（n=1）和胸腺（n=1），靶病灶位于肝脏（n=7）、骨（n=2）、原发部位（n=1）、淋巴结（n=1）和腹膜（n=1）。12对血清包括10对单次PRRT给药前后样本和2对全疗程前后样本。在检测的36种细胞因子中，仅12种可检出。其中，CD154在7对中显示出2倍以上的变化，PRRT后6对下调、1对上调。IL-1ra在3对中也上调。
结论：我们发现PRRT与NET患者循环细胞因子的全身性变化相关，尤其是CD154和IL-1ra的调节。这些数据提示PRRT可能影响宿主抗肿瘤免疫；需要更大规模的研究来阐明这些免疫变化的机制和临床意义。
查看英文原文 English abstract
Background: Peptide receptor radionuclide therapy (PRRT) is an internal radiotherapy for somatostatin receptor (SSTR)-positive neuroendocrine tumor (NET). The tumor microenvironment, particularly cytotoxic T lymphocyte (CTL), is a key determinant of tumor behavior, treatment response, and prognosis, but NET typically shows a “cold” immune microenvironment with sparse immune-cell infiltration, which may contribute to the limited efficacy of ICI-based therapies. External beam radiotherapy can activate systemic antitumor immunity and occasionally induce abscopal effects, in which irradiation of a primary lesion leads to shrinkage of both irradiated and distant metastatic sites; however, the influence of PRRT on systemic immunity has scarcely been studied. We hypothesized that PRRT modulates systemic immunity in NET patients and investigated changes in circulating cytokines.
Methods: We analyzed changes in serum cytokine levels in NET patients treated with PRRT at Yokohama City University. Twelve paired serum samples from 9 patients were collected before and after PRRT and analyzed with a 36-plex cytokine array.
Results: Of the 9 patients, 7 were undergoing their first PRRT course and 2 a second course (retreatment after a prior four-administration PRRT course that had achieved at least partial response with ≥1.5 year of disease control). Primary sites were pancreas (n=6), rectum (n=1), lung (n=1), and thymus (n=1), and target lesions were in the liver (n=7), bone (n=2), primary site (n=1), lymph node (n=1), and peritoneum (n=1). Twelve serum pairs comprised 10 pre- and post-individual PRRT administrations and 2 pre- and post-full-course pairs. Of the 36 examined cytokines, only 12 were detectable. Among these, CD154 showed more than 2-fold changes in 7 pairs, with 6 showing downregulation and 1 showing upregulation after PRRT. IL-1ra was also upregulated in 3 pairs.
Conclusion: We found that PRRT is associated with systemic changes in circulating cytokines in NET patients, notably modulation of CD154 and IL-1ra. These data suggest that PRRT may influence host antitumor immunity; larger studies are required to elucidate the mechanisms and clinical significance of these immune changes.
利益披露 Disclosure
E. Katsuta, None..
T. Nobuhiro, None..
M. Takeuchi, None..
S. Matsui, None..
A. Daisuke, None..
I. Yoshiya, None..
H. Ueda, None..
K. Akahoshi, None..
N. Kobayashi, None..
Y. Ichikawa, None..
D. Ban, None.