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结直肠癌转移过程中 PD-L1 表达的上调:免疫治疗的意义。

Rise of PD-L1 expression during metastasis of colorectal cancer: Implications for immunotherapy.

机构信息

Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, State Key Laboratory for Oncogenes and Related Genes, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, Shanghai, China.

出版信息

J Dig Dis. 2017 Oct;18(10):574-581. doi: 10.1111/1751-2980.12538.

DOI:10.1111/1751-2980.12538
PMID:28851046
Abstract

OBJECTIVE

Programmed death-ligand 1 (PD-L1) expression in colorectal cancer (CRC) was implicated in predicting anti-PD-1/PD-L1 therapy efficacy. However, therapeutic response has also been found in patients without PD-L1 expression in the primary tumor. In the present study, we aimed to clarify the prevalence of PD-L1 in primary and metastatic CRC.

METHODS

The expression of PD-L1 was determined by immunohistochemistry in matched primary and metastatic CRC.

RESULTS

PD-L1 expression was significantly more prevalent in metastatic CRCs than in primary tumors, and the expression of PD-L1 in primary CRC may not represent the tumors that spread to distant organs. Positive expression of PD-L1 was found in 81.8% of metastatic CRC, being significantly more prevalent than in primary CRC (40.9%; P = 0.012, Fisher's exact test). While comparing the primary and metastatic lesions of the same patients, we found that PD-L1 expression frequently increased during the metastatic process. However, PD-L1 expression was rarely decreased in metastatic lesions. Intratumoral heterogeneity expression of PD-L1 was found in both metastatic CRC (22.2%) and primary CRCs (33.3%). PD-L1 was prevalently expressed in metastatic CRC, and increased PD-L1 expression was frequently found in metastatic CRC as compared to primary tumors.

CONCLUSION

PD-L1 expression in metastatic CRC should be considered as an independent factor while evaluating the suitability of patients for immunotherapy.

摘要

目的

程序性死亡配体 1(PD-L1)在结直肠癌(CRC)中的表达与预测抗 PD-1/PD-L1 治疗疗效有关。然而,也发现在原发性肿瘤中没有 PD-L1 表达的患者中存在治疗反应。本研究旨在阐明 PD-L1 在原发性和转移性 CRC 中的流行情况。

方法

通过免疫组织化学法检测匹配的原发性和转移性 CRC 中 PD-L1 的表达。

结果

转移性 CRC 中 PD-L1 的表达明显高于原发性肿瘤,而原发性 CRC 中 PD-L1 的表达可能不能代表转移到远处器官的肿瘤。转移性 CRC 中 PD-L1 的阳性表达率为 81.8%,明显高于原发性 CRC(40.9%;P=0.012,Fisher 确切检验)。在比较同一患者的原发性和转移性病变时,我们发现 PD-L1 表达在转移过程中经常增加。然而,转移性病变中 PD-L1 表达很少减少。转移性 CRC(22.2%)和原发性 CRCs(33.3%)中均发现 PD-L1 的肿瘤内异质性表达。转移性 CRC 中 PD-L1 表达普遍存在,与原发性肿瘤相比,转移性 CRC 中 PD-L1 表达增加更为常见。

结论

在评估患者免疫治疗的适宜性时,应将转移性 CRC 中的 PD-L1 表达视为一个独立因素。

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