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CD200 在胰腺癌中的临床意义和治疗意义

英文原题:Clinical significance and therapeutic implication of CD200 in pancreatic cancer.

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Clinical significance and therapeutic implication of CD200 in pancreatic cancer.

PubMed 2024/10/12(内容时间) Pancreatology Q2 · IF 3.9(JCR 2025)

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研究概要

我们的数据强调了 CD200 在胰腺癌免疫逃逸及治疗耐药中的新作用。CD200 可能代表 PDAC 接受 NACRT 的一种新的不良预后预测因素和潜在治疗靶点。

研究思路结论见上方概要

CD200作为T细胞的负调控因子以及癌症干细胞的标志物,在某些癌症中是一个重要的预后因素和潜在治疗靶点。然而,其在胰腺导管腺癌(PDAC)中的临床意义仍不清楚。

在220例接受手术切除的PDAC患者中评估了CD200,这些患者接受了伴或不伴新辅助放化疗(NACRT)的手术治疗。我们研究了与CD200相关的临床病理结局,并进一步评估了其在免疫学和癌症干细胞特性方面的临床意义。

NACRT与更高的CD200表达相关(66.4 % vs. 32.2 %,P < 0.001),相比直接手术。CD200被确定为NACRT的独立不良预后因素(风险比1.90,95 %置信区间1.12-3.23,P = 0.016),但在直接手术患者中则不是。在NACRT组中,CD200+患者的复发后生存显著差于CD200-患者,而在直接手术组中未观察到显著差异。CD200表达与显著较低的CD4 +、CD8 + 和CD45RO + TIL(肿瘤浸润淋巴细胞)水平相关。此外,在照射的人胰腺癌细胞中,CD200与胰腺癌干细胞标志物CD44/CD24/ESA的相关性更强。

展开英文摘要原文

CD200, a negative regulator of T cells as well as a marker for cancer stem cells, represents a significant prognostic factor and potential therapeutic target in certain cancers. However, its clinical significance remains unknown in pancreatic ductal adenocarcinoma (PDAC).

CD200 was assessed in 220 resected PDAC patients who underwent surgery with or without neoadjuvant chemoradiotherapy (NACRT). We examined the clinicopathological outcomes associated with CD200 and further assessed its clinical implications regarding immunological and cancer stem cell properties.

NACRT was associated with higher CD200 expression (66.4 % vs. 32.2 %, P < 0.001) compared to upfront surgery. CD200 was identified as an independent poor prognostic factor in NACRT (hazard ratio 1.90, 95 % confidence interval 1.12-3.23, P = 0.016), but not in upfront surgery patients. Post-recurrence survival was significantly worse in CD200+ patients compared to CD200- patients in the NACRT group, but there was no significant difference observed in the upfront surgery group. CD200 expression was correlated with significantly lower levels of CD4 + , CD8 + , and CD45RO + tumor-infiltrating lymphocytes. Furthermore, the correlation of CD200 with pancreatic cancer stem cell markers CD44/CD24/ESA was stronger in irradiated human pancreatic cancer cells.

Our data underscore novel roles for CD200 in immune evasion as well as therapy resistance in pancreatic cancer. CD200 may represent a novel poor prognostic predictive factor and potential therapeutic target for PDAC with NACRT.

论文信息

作者
Kinoshita S、Terai T、Nagai M、Nakamura K、Kohara Y、Yasuda S、Matsuo Y、Doi S
第一作者单位
Department of Surgery, Nara Medical University, 840 Shijo-cho, Kashihara, Nara, 634-8522, Japan.Japan
通讯作者单位
Department of Surgery, Nara Medical University, 840 Shijo-cho, Kashihara, Nara, 634-8522, Japan. Electronic address: m-sho@naramed-u.ac.jp.Japan
期刊
Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.]2024 Dec
原文标识
PubMed 39419752 · DOI 10.1016/j.pan.2024.10.007