PD-L1 CD8+和CD4+淋巴细胞率预测胸段食管鳞癌新辅助放化疗后病理完全缓解

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Title

PD‐L1 expression, CD8+ and CD4+ lymphocyte rate are predictive of pathological complete response after neoadjuvant chemoradiotherapy for squamous cell cancer of the thoracic esophagus

Background

Neoadjuvant chemoradiotherapy (CTRT) can effectively downstage esophageal squamous cell carcinoma (SCC) in patients with locally advanced disease and prolonged survival have been observed in patients with a pathological complete response (ypCR).

新辅助放化疗（CTRT）可有效实现局部进展食管鳞癌（SCC）患者肿瘤降期并延长获得病理完全缓解（ypCR）食管鳞癌患者的生存期。

Aims and methods

This exploratory study aimed to identify immunological predictors of pCR after neoadjuvant CTRT within SCC microenvironment. The tumor regression after neoadjuvant therapy was measured according to the Mandard score system. Eighty‐eight consecutive patients with SCC of the thoracic esophagus who received neoadjuvant CTRT were included in this retrospective study.

本探索性研究旨在鉴别出SCC新辅助CTRT后获得pCR患者微环境的免疫预测因子。使用Mandard分级系统评价肿瘤退缩情况。本回顾性研究纳入了88例接受了新辅助CTRT的胸段食管鳞癌患者。

Inclusion criteria were neoadjuvant CTRT and the availability of representative histological samples taken at diagnosis. We investigated immunohistochemical expression of CD4, Tbet, FoxP3, CD8, CD80, PD‐L1, and PD‐1, in the pretreatment biopsies and correlated the immunohistochemical profiles to patients’ outcomes.

纳入标准是新辅助CTRT和诊断时取得明确的病理学标本。我们在预处理组织活检时检测了CD4、Tbet、FoxP3、CD8、CD80、PD‐L1和 PD‐1并将免疫组化图表与患者结局相关联。

Results

After neoadjuvant CTRT, 23 patients had pCR, while 65 ones had partial response, stable disease or progression. PD‐L1 expression and CD8+ and CD4+ lymphocyte rate were significantly higher in patients who had ypCR compared to those who had not (10 (0‐55) vs 0 (0‐0),P=0.004, 73 (36‐147) vs 21 (7‐47),P=0.0006 and 39 (23‐74) vs 5 (0‐13),P<0.0001 respectively).

在接受新辅助CTRT后，23例患者达到pCR，65例部分缓解/病变稳定/进展。ypCR患者的PD-L1表达、CD8+ 和 CD4+淋巴细胞率显着高于非ypCR患者(分别为：10 (0‐55) vs 0 (0‐0), P =0.004, 73 (36‐147) vs 21 (7‐47), P =0.0006 和39 (23‐74) vs 5 (0‐13), P <0.0001 )。

The accuracy of expression of PD‐L1+, CD8+, and CD4+ lymphocyte rate in identifying responders was AUC=0.76 (P=0.001), AUC=0.81 (P=0.0001) and AUC=0.75 (P=0.0001), respectively. Within the ypCR group, all patients with high infiltration of CD4+ T cell recurred/relapsed while only the 38.9% of those with low CD4+ T cell infiltration did the same (P=0.058).

在鉴定治疗有应答患者中PD-L1 +，CD8 +和CD4 +淋巴细胞率的表达准确度分别为AUC = 0.76（P = 0.001），AUC = 0.81（P = 0.0001）和AUC = 0.75（P = 0.0001）。在ypCR组中，所有CD4 + T细胞浸润率高的患者肿瘤复发，而CD4 + T细胞浸润率低的患者仅有38.9％（P = 0.058）。

Conclusions

PD‐L1 expression and CD8+ and CD4+ lymphocyte rate were predictive of ypCR after neoadjuvant CTRT for SCC of the thoracic esophagus with adequate accuracy. Furthermore, recurrence/relapse was associated with high level of CD4+ T cell infiltration. However, the small sample size prevented to draw definitive conclusions; further studies are necessary to evaluate the prognostic role of these markers.

PD-L1表达和CD8 +和CD4 +淋巴细胞率对接受新辅助CTRT后胸段食管SCC患者的ypCR预测具有足够的准确性。此外，肿瘤复发与高水平的CD4 + T细胞浸润有关。然而，小样本量无法得出明确的结论; 需要进一步的研究来评估这些标志物的预后作用。

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