Inoue Yuka, Hazama Shoichi, Suzuki Nobuaki, Tokumitsu Yukio, Kanekiyo Shinsuke, Tomochika Shinobu, Tsunedomi Ryouichi, Tokuhisa Yoshihiro, Iida Michihisa, Sakamoto Kazuhiko, Takeda Shigeru, Ueno Tomio, Yoshino Shigefumi, Nagano Hiroaki
Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan.
Department of Translational Research and Developmental Therapeutics against Cancer, Yamaguchi University School of Medicine, Ube, Yamaguchi, Japan.
Cancer Sci. 2017 Mar;108(3):455-460. doi: 10.1111/cas.13162.
Cetuximab has activity against colorectal cancers. Recent studies demonstrated that cetuximab induces antibody-dependent cell-mediated cytotoxicity via immune cells, and a new immune-related mechanism of inducing immunogenic cell death. This study aimed to evaluate the immune responses induced by cetuximab in tumor microenvironments at liver metastasis sites of metastatic colorectal cancer patients. We assessed immune cell infiltration in the liver metastatic sites of 53 colorectal cancer patients. These patients were divided into three groups according to the treatment before operation: chemotherapy with cetuximab, chemotherapy without cetuximab, and no chemotherapy. The inflammatory cells in the liver metastatic sites were assessed by hematoxylin-eosin staining, focusing on the invasive margin. The overall inflammatory reaction and number of lymphoid cells were assessed with a four-point scoring system. We then assessed immune cell infiltration (CD3, CD8 and CD56) in 15 liver metastatic sites. Hematoxylin-eosin staining demonstrated more inflammatory cells in the chemotherapy with cetuximab group than in the other groups (P < 0.001). Of note, inflammatory cells were found in intratumoral areas, and the destruction of cancer cell foci was observed in the chemotherapy with cetuximab group. Moreover, a higher infiltration of CD3+ (P = 0.003), CD8+ (P = 0.003) and CD56+ (P = 0.001) cells was observed in the chemotherapy with cetuximab group than in the other groups. These results suggest that cetuximab might have an immune-enhancing effect. As such, the immune-related mechanism of action of cetuximab may enhance the efficacy of combination therapy, such as chemotherapy and immunotherapy using therapeutic peptides.
西妥昔单抗对结直肠癌具有活性。最近的研究表明，西妥昔单抗通过免疫细胞诱导抗体依赖性细胞介导的细胞毒性，以及一种诱导免疫原性细胞死亡的新的免疫相关机制。本研究旨在评估西妥昔单抗在转移性结直肠癌患者肝转移部位肿瘤微环境中诱导的免疫反应。我们评估了53例结直肠癌患者肝转移部位的免疫细胞浸润情况。这些患者根据术前治疗分为三组：西妥昔单抗化疗组、非西妥昔单抗化疗组和未化疗组。通过苏木精-伊红染色评估肝转移部位的炎症细胞，重点关注浸润边缘。采用四点评分系统评估总体炎症反应和淋巴细胞数量。然后我们评估了15个肝转移部位的免疫细胞浸润情况（CD3、CD8和CD56）。苏木精-伊红染色显示，西妥昔单抗化疗组的炎症细胞比其他组更多（P < 0.001）。值得注意的是，在肿瘤内区域发现了炎症细胞，并且在西妥昔单抗化疗组中观察到癌细胞灶的破坏。此外，西妥昔单抗化疗组中观察到的CD3+（P = 0.003）、CD8+（P = 0.003）和CD56+（P = 0.001）细胞浸润高于其他组。这些结果表明西妥昔单抗可能具有免疫增强作用。因此，西妥昔单抗的免疫相关作用机制可能会提高联合治疗的疗效，如使用治疗性肽的化疗和免疫治疗。
