Koemans Willem J, van Dieren Jolanda M, van den Berg Jose G, Meijer Gerrit A, Snaebjornsson Petur, Chalabi Myriam, Lecot Frederig, Riedl Robert, Krijgsman Oscar, Hofland Ingrid, Broeks Annegien, Voncken Francine E M, Peppelenbosch Maikel P, Sosef Meindert N, van Sandick Johanna W, Kodach Liudmila L
Department of Surgical Oncology, Antoni van Leeuwenhoek, the Netherlands Cancer Institute, Amsterdam, the Netherlands.
Department of Gastrointestinal Oncology, Antoni van Leeuwenhoek, the Netherlands Cancer Institute, Amsterdam, the Netherlands.
Histopathology. 2021 Aug;79(2):238-251. doi: 10.1111/his.14361. Epub 2021 Apr 27.
Determining prognosis following poor response to neoadjuvant chemoradiotherapy (nCRT) in oesophageal adenocarcinoma (OAC) remains challenging. An immunosuppressive tumour microenvironment (TME) as well as immune infiltrate density and composition are considered to play a critical role in the immune interaction between host and tumour and can predict therapy response and survival in many cancers, including gastrointestinal malignancies. The aim of this study was to establish the TME characteristics associated with survival following a poor response to nCRT.
The prognostic significance of OAC-associated CD3 , CD4 , CD8 , forkhead box protein 3 (FoxP3 ) and programmed cell death ligand 1 (PD-L1) expression was studied by immunohistochemistry and quantified by automated image analysis in 123 patients who underwent nCRT and curative resection. Results from good and poor responders were contrasted and immune infiltration was related to disease course in both groups. Subsequently a cohort of 57 patients with a moderate response to nCRT was analysed in a similar fashion. Tumour cell percentage positively correlated to immune infiltration markers. In good and moderate responders, none of the immune infiltrate parameters was associated with survival; in poor responders CD8 was an independent negative predictor of OS in univariate analysis (P = 0.03) and high CD8 infiltration was associated with worse OS (15 versus 32 months, P = 0.042).
A high CD8 density is an independent biomarker of poor OS in poor responders to nCRT, but not in good and moderate responders. Our results suggest that patients with a poor response to nCRT but concomitant high CD8 counts in the resection specimen require adjuvant therapy.
确定食管腺癌（OAC）新辅助放化疗（nCRT）疗效不佳后的预后仍然具有挑战性。免疫抑制性肿瘤微环境（TME）以及免疫浸润密度和组成被认为在宿主与肿瘤之间的免疫相互作用中起关键作用，并且可以预测包括胃肠道恶性肿瘤在内的许多癌症的治疗反应和生存情况。本研究的目的是确定与nCRT疗效不佳后的生存相关的TME特征。
通过免疫组织化学研究OAC相关的CD3、CD4、CD8、叉头框蛋白3（FoxP3）和程序性细胞死亡配体1（PD-L1）表达的预后意义，并通过自动图像分析对123例行nCRT和根治性切除的患者进行定量分析。对比了反应良好和反应不佳者的结果，并分析了两组中免疫浸润与病程的关系。随后，以类似方式分析了57例对nCRT反应中等的患者队列。肿瘤细胞百分比与免疫浸润标志物呈正相关。在反应良好和中等的患者中，没有免疫浸润参数与生存相关；在反应不佳的患者中，CD8在单因素分析中是总生存期（OS）的独立负性预测因子（P = 0.03），高CD8浸润与较差的OS相关（15个月对32个月，P = 0.042）。
高CD8密度是nCRT反应不佳患者OS不良的独立生物标志物，但在反应良好和中等的患者中并非如此。我们的结果表明，nCRT反应不佳但切除标本中CD8计数高的患者需要辅助治疗。
