Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan.
Department of Clinical Research in Tumor Immunology, Osaka University Graduate School of Medicine, Osaka, Japan.
Cancer Sci. 2020 Apr;111(4):1103-1112. doi: 10.1111/cas.14328. Epub 2020 Feb 18.
The association between the tumor microenvironment (TME) and treatment response or survival has been a recent focus in several types of cancer. However, most study materials are resected specimens that were completely modified by prior chemotherapy; therefore, the unmodified host immune condition has not yet been clarified. The aim of the present study was to evaluate the relationship between TME assessed in pre-therapeutic biopsy samples and chemoresistance in esophageal cancer (EC). A total of 86 endoscopic biopsy samples from EC patients who received neoadjuvant chemotherapy (NAC) prior to surgery were evaluated for the number of intratumoral CD4 lymphocytes (with/without Foxp3 expression), CD8 lymphocytes (with/without PD-1 expression), monocytes (CD14 ) and macrophages (CD86 , CD163 and CD206 ) by multiplex immunohistochemistry (IHC). The number of tumor-infiltrating CD206 macrophages I significantly correlated with cT, cM, cStage and neutrophil/lymphocyte ratio (NLR), whereas the number of lymphocytes (including expression of Foxp3 and PD-1) was not associated with clinico-pathological features. The high infiltration of CD163 or CD206 macrophages was significantly associated with poor pathological response to NAC (P = 0.0057 and 0.0196, respectively). Expression of arginase-1 in CD163 macrophages tended to be higher in non-responders (29.4% vs 18.2%, P = 0.17). In addition, patients with high infiltration of M2 macrophages exhibited unfavorable overall survival compared to those without high infiltration of M2 macrophages (5-year overall survival 57.2% vs 71.0%, P = 0.0498). Thus, a comprehensive analysis of TME using multiplex IHC revealed that M2 macrophage infiltration would be useful in predicting the response to NAC and long-term survival in EC patients.
肿瘤微环境（TME）与治疗反应或生存之间的关联一直是几种类型癌症的近期研究重点。然而，大多数研究材料是经过先前化疗完全修饰的切除标本；因此，未修饰的宿主免疫状态尚未阐明。本研究旨在评估治疗前活检样本中 TME 评估与食管癌（EC）化疗耐药之间的关系。共评估了 86 例接受新辅助化疗（NAC）术前的 EC 患者的内镜活检样本，通过多重免疫组化（IHC）评估肿瘤内 CD4 淋巴细胞（有/无 Foxp3 表达）、CD8 淋巴细胞（有/无 PD-1 表达）、单核细胞（CD14）和巨噬细胞（CD86、CD163 和 CD206）的数量。肿瘤浸润性 CD206 巨噬细胞的数量与 cT、cM、cStage 和中性粒细胞/淋巴细胞比值（NLR）显著相关，而淋巴细胞（包括 Foxp3 和 PD-1 的表达）的数量与临床病理特征无关。CD163 或 CD206 巨噬细胞的高浸润与 NAC 病理反应不良显著相关（P=0.0057 和 0.0196）。CD163 巨噬细胞中精氨酸酶-1 的表达在无反应者中趋于更高（29.4%比 18.2%，P=0.17）。此外，高浸润 M2 巨噬细胞的患者总生存情况不如无 M2 巨噬细胞高浸润的患者（5 年总生存率 57.2%比 71.0%，P=0.0498）。因此，使用多重 IHC 对 TME 进行综合分析表明，M2 巨噬细胞浸润有助于预测 EC 患者对 NAC 的反应和长期生存。
