Kataoka Jun, Takenouchi Kazumasa, Suzuki Toshihiro, Ohnuki Kazunobu, Tsukada Yuichiro, Gotohda Naoto, Ito Masaaki, Nakatsura Tetsuya
Division of Cancer Immunotherapy, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, 6-5-1 Kashiwanoha, Kashiwa 277-8577, Japan.
Department of Colorectal Surgery, National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa 277-8577, Japan.
Int J Mol Sci. 2025 Jul 31;26(15):7402. doi: 10.3390/ijms26157402.
Stage IV colorectal cancer has a poor prognosis, and liver metastases are prone to recurrence, even after resection. This study aimed to identify common cancer antigens, using immunohistochemical staining, as promising targets for antigen-specific immunotherapies in colorectal cancer. We analyzed expression levels and intracellular localization of seven common cancer antigens, CLDN1, EphB4, LAT1, FOXM1, HSP105α, ROBO1, and SPARC, and human leukocyte antigen (HLA) class I via immunohistochemical staining of 85 surgical specimens from primaries and liver metastases. Staining intensity and positive staining were scored to evaluate antigen expression. In 25 primaries, seven cancer antigens were expressed in 88-96% of cases, while HLA class I was expressed on the cell membrane in 80.0% of cases. In 60 liver metastases, FOXM1 and SPARC expression were approximately half that observed in the primaries. Other antigens and HLA class I were highly expressed in both. Most of the primaries and liver metastases may benefit from chimeric antigen receptor-T cell therapy targeting CLDN1, EphB4, and LAT1. Cases with high HLA class I expression may be suitable for vaccine-based and T cell receptor-T cell therapy targeting CLDN1, EphB4, LAT1, FOXM1, HSP105α, ROBO1, and SPARC for primaries and targeting antigens, excluding FOXM1 and SPARC, for liver metastases.
IV期结直肠癌预后较差，即使在切除术后，肝转移仍易于复发。本研究旨在通过免疫组织化学染色鉴定常见癌症抗原，作为结直肠癌抗原特异性免疫疗法的潜在靶点。我们通过对85例原发灶和肝转移灶手术标本进行免疫组织化学染色，分析了7种常见癌症抗原CLDN1、EphB4、LAT1、FOXM1、HSP105α、ROBO1和SPARC以及人类白细胞抗原（HLA）I类分子的表达水平和细胞内定位。对染色强度和阳性染色进行评分以评估抗原表达。在25例原发灶中，7种癌症抗原在88%-96%的病例中表达，而HLA I类分子在80.0%的病例中在细胞膜上表达。在60例肝转移灶中，FOXM1和SPARC的表达约为原发灶中的一半。其他抗原和HLA I类分子在两者中均高表达。大多数原发灶和肝转移灶可能受益于靶向CLDN1、EphB4和LAT1的嵌合抗原受体T细胞疗法。HLA I类分子高表达的病例可能适合基于疫苗的疗法以及针对原发灶的靶向CLDN1、EphB4、LAT1、FOXM1、HSP105α、ROBO1和SPARC以及针对肝转移灶的排除FOXM1和SPARC外的靶向抗原的T细胞受体T细胞疗法。
