Clinical significance and therapeutic implication of CD200 in pancreatic cancer.

IF 2.8 2区医学 Q2 GASTROENTEROLOGY & HEPATOLOGY Pancreatology Pub Date : 2024-10-12 DOI:10.1016/j.pan.2024.10.007

Shoichi Kinoshita, Taichi Terai, Minako Nagai, Kota Nakamura, Yuichiro Kohara, Satoshi Yasuda, Yasuko Matsuo, Shunsuke Doi, Takeshi Sakata, Kazuhiro Migita, Noriko Ouji-Sageshima, Toshihiro Ito, Masayuki Sho

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Abstract

Background: 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).

Methods: 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.

Results: 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.

Conclusions: 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.

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CD200 在胰腺癌中的临床意义和治疗作用。

背景：CD200是T细胞的负调控因子，也是癌症干细胞的标记物，是某些癌症的重要预后因素和潜在治疗靶点。然而，CD200在胰腺导管腺癌（PDAC）中的临床意义尚不清楚：方法：我们对 220 例切除的 PDAC 患者的 CD200 进行了评估，这些患者接受了手术，并接受或不接受新辅助化放疗（NACRT）。我们研究了与CD200相关的临床病理结果，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：结果：NACRT 与较高的 CD200 表达有关（66.4% 对 32.2%，P +、CD8+ 和 CD45RO+ 肿瘤浸润淋巴细胞）。此外，CD200与胰腺癌干细胞标记物CD44/CD24/ESA的相关性在受照射的人类胰腺癌细胞中更强：我们的数据强调了 CD200 在胰腺癌免疫逃避和耐药性中的新作用。结论：我们的数据强调了 CD200 在胰腺癌免疫逃避和耐药性中的新作用，CD200 可能是一种新的不良预后预测因子，也是 NACRT 治疗 PDAC 的潜在治疗靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Pancreatology 医学-胃肠肝病学

CiteScore

7.20

自引率

5.60%

发文量

194

审稿时长

44 days

期刊介绍： Pancreatology is the official journal of the International Association of Pancreatology (IAP), the European Pancreatic Club (EPC) and several national societies and study groups around the world. Dedicated to the understanding and treatment of exocrine as well as endocrine pancreatic disease, this multidisciplinary periodical publishes original basic, translational and clinical pancreatic research from a range of fields including gastroenterology, oncology, surgery, pharmacology, cellular and molecular biology as well as endocrinology, immunology and epidemiology. Readers can expect to gain new insights into pancreatic physiology and into the pathogenesis, diagnosis, therapeutic approaches and prognosis of pancreatic diseases. The journal features original articles, case reports, consensus guidelines and topical, cutting edge reviews, thus representing a source of valuable, novel information for clinical and basic researchers alike.