JUNE 7,2019
ASCO快递
结直肠癌是全球第三大最常见的男性癌症，和第二大女性癌症。近年来，PD-1/PD-L1等免疫检查点分子已被确定为CRC免疫治疗的可能靶点，并越来越多地与化疗联合进行临床试验。然而，PD-L1表达在CRC肿瘤细胞中的作用及其与其他临床病理因素的相互作用尚不清楚。2019年ASCO会议中，来自波兰的研究学者报导了新辅助化疗对PD-L1阳性循环上皮肿瘤细胞（CETCs）分数的影响，并将其表达与原发肿瘤进行比较。
01
研究方法
在本项研究中，研究人员从20例不同分期的结直肠癌患者的血液中检测出CETCs。采用maintrac方法研究CETCs的数量及其PD-L1的表达。同时，采用组织活检的免疫组织化学方法检测PD-L1表达和肿瘤浸润淋巴细胞(TILs)。
02
研究结果
研究结果发现，PD-L1的表达可以在所有检测到CETCs的患者中进行评估，中位数为50%。相对于组织，CETCs中PD-L1阳性表达的频率较高，组织与CETCs中PD-L1表达无相关性。有趣的是，新辅助化疗组的PD-L1 CETCs阳性率高于未化疗组(平均值66,7 vs. 35,2 p < 0.05)，但新辅助化疗组的CETCs总数明显低于未化疗组。此外，与其他组织学亚型相比，粘液腺癌患者有更多的PD-L1阳性CETCs。淋巴结转移和肿瘤体积较大的患者TILs数较高。在接受和不接受新辅助化疗的患者中，TILs计数没有差异。
03
结果分析
该项结果表明，在新辅助治疗中增加免疫治疗可能是大肠癌(CRC)治疗是有效的方案，特别是对于新辅助化疗后程序性细胞死亡配体-1 (PD-L1)阳性CETC水平较高的患者。评估PD-L1在CETCs中的表达是可行的，而且CETCs通常比在组织中阳性更高。在接受新辅助化疗的患者中，CETCs上PD-L1表达较高。
Background: CRC is the third most frequent cancer in men and second in women worldwide. Recently, immune checkpoint molecules such as PD-1/PD-L1 have been identified as a possible target for immunotherapy in CRC and are increasingly being tested in clinical trials in combination with chemotherapy. However, the role of PD-L1 expression in CRC tumor cells and its interaction with other clinicopathologic factors remains elusive. In this study, we evaluated the impact of neoadjuvant chemotherapy on the fraction of PD-L1 positive CETCs and to compare its expression to the primary tumor.
Methods: CETCs were determined from the blood of 20 patients suffering from CRC in different stages of the disease. The number of CETCs and their expression of PD-L1 were investigated using the maintrac method. In parallel, PD-L1 expression and tumor infiltrating lymphocytes (TILs) were assessed by immunohistochemistry on tissue biopsies. Results: PD-L1 expression could be assessed in all patients with detectable CETCs with a median of 50%. CETCs were more frequently found to be PD-L1 positive than tissue, and no correlation was observed between tissue and CETCs PD-L1 expression. Interestingly, patients with neoadjuvant chemotherapy had more positive PD-L1 CETCs compared to patients without chemotherapy (mean 66,7 vs. 35,2 p < 0.05), but the total number of CETCs was significantly lower in the neoadjuvant group. Also, patients with mucinous adenocarcinoma had more PD-L1 positive CETCs compared to other histological subtypes. The number of TILs was higher in patients with lymph node metastasis and larger tumors. TILs count did not differ in patients with and without neoadjuvant chemotherapy.
Conclusions: Assessment of PD-L1 expression in CETCs is feasible, and CETCs are more often positive than in tissue. PD-L1 expression on CETCs was higher in patients who received neoadjuvant chemotherapy. Further studies are necessary to validate these findings.
原文链接：http://abstracts.asco.org/239/AbstView_239_262911.html
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