Creatv MicroTech, Inc., Monmouth Junction, New Jersey.
Rutgers, the State University of New Jersey, New Brunswick, New Jersey.
Clin Cancer Res. 2017 Oct 1;23(19):5948-5958. doi: 10.1158/1078-0432.CCR-17-0802. Epub 2017 Jul 5.
Evidence suggests that PD-L1 can be induced with radiotherapy and may be an immune escape mechanism in cancer. Monitoring this response is limited, as repetitive biopsies during therapy are impractical, dangerous, and miss tumor stromal cells. Monitoring PD-L1 expression in both circulating tumor cells (CTCs) and circulating stromal cells (CStCs) in blood-based biopsies might be a practical alternative for sequential, noninvasive assessment of changes in tumor and stromal cells. Peripheral blood was collected before and after radiotherapy from 41 patients with lung cancer, as were primary biopsies. We evaluated the expression of PD-L1 and formation of RAD50 foci in CTCs and a CStC subtype, cancer-associated macrophage-like cells (CAMLs), in response to DNA damage caused by radiotherapy at the tumor site. Only 24% of primary biopsies had sufficient tissue for PD-L1 testing, tested with IHC clones 22c3 and 28-8. A CTC or CAML was detectable in 93% and 100% of samples, prior to and after radiotherapy, respectively. RAD50 foci significantly increased in CTCs (>7×, < 0.001) and CAMLs (>10×, = 0.001) after radiotherapy, confirming their origin from the radiated site. PD-L1 expression increased overall, 1.6× in CTCs ( = 0.021) and 1.8× in CAMLs ( = 0.004): however, individual patient PD-L1 expression varied, consistently low/negative (51%), consistently high (17%), or induced (31%). These data suggest that RAD50 foci formation in CTCs and CAMLs may be used to track cells subjected to radiation occurring at primary tumors, and following PD-L1 expression in circulating cells may be used as a surrogate for tracking adaptive changes in immunotherapeutic targets. .
有证据表明，PD-L1 可以通过放射治疗诱导产生，并且可能是癌症中的一种免疫逃逸机制。然而，这种反应的监测受到限制，因为在治疗过程中重复进行活检既不切实际，又危险，而且会遗漏肿瘤基质细胞。通过血液活检监测循环肿瘤细胞（CTCs）和循环基质细胞（CStCs）中 PD-L1 的表达，可能是一种实用的替代方法，可用于连续、非侵入性评估肿瘤和基质细胞的变化。从 41 名肺癌患者中采集了放射治疗前后的外周血和原发性活检样本。我们评估了 PD-L1 的表达以及 CTCs 和 CStC 亚型——癌症相关巨噬细胞样细胞（CAMLs）中 RAD50 焦点的形成，以响应肿瘤部位放射治疗引起的 DNA 损伤。只有 24%的原发性活检有足够的组织进行 PD-L1 检测，使用 IHC 克隆 22c3 和 28-8 进行检测。在放射治疗前后，分别有 93%和 100%的样本可检测到 CTC 或 CAML。放射治疗后，CTC 中 RAD50 焦点显著增加（>7×，<0.001），CAML 中 RAD50 焦点显著增加（>10×，=0.001），证实其来源于辐射部位。PD-L1 表达总体上增加，CTC 中增加 1.6 倍（=0.021），CAML 中增加 1.8 倍（=0.004）：然而，个别患者的 PD-L1 表达存在差异，持续低/阴性（51%）、持续高（17%）或诱导（31%）。这些数据表明，CTC 和 CAML 中 RAD50 焦点的形成可用于跟踪发生在原发性肿瘤的放射细胞，并且循环细胞中 PD-L1 的表达可作为跟踪免疫治疗靶点适应性变化的替代指标。
