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Takenouchi, K.; Suzuki, T.; Ohnuki, K.; Tsukada, Y.; Gotohda, N.; Ito, M.; Nakatsura, T. Identification of Common Cancer Antigens Useful for Specific Immunotherapies to Colorectal Cancer and Liver Metastases. Int. J. Mol. Sci. 2025, 26, 7402. [https://](https://)[ ](https://)[doi.org/10.3390/ijms26157402](doi.org/10.3390/ijms26157402)  \n[Copyright:](Copyright:) © 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://creativecommons.org/](https://creativecommons.org/)[ ](https://creativecommons.org/)[licenses/by/4.0/](licenses/by/4.0/)) .  \n1 Division of Cancer Immunotherapy, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, 6-5-1 Kashiwanoha, Kashiwa 277-8577, Japan; [jkataoka@east.ncc.go.jp](jkataoka@east.ncc.go.jp) (J.K.); [katakeno@east.ncc.go.jp](katakeno@east.ncc.go.jp) (K.T.); [toshsuzu@east.ncc.go.jp](toshsuzu@east.ncc.go.jp) (T.S.); [konuki@east.ncc.go.jp](konuki@east.ncc.go.jp) (K.O.)  \n2 Department of Colorectal Surgery, National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa 277-8577, Japan; [yutsukad@east.ncc.go.jp](yutsukad@east.ncc.go.jp) (Y.T.); [maito@east.ncc.go.jp](maito@east.ncc.go.jp) (M.I.)  \n3 Course of Advanced Clinical Research of Cancer, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan; [ngotohda@east.ncc.go.jp](ngotohda@east.ncc.go.jp)  \n4 Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa 277-8577, Japan  \n* Correspondence: [tnakatsu@east.ncc.go.jp](tnakatsu@east.ncc.go.jp); Tel.: +81-4-7131-5490  \nAbstract  \nStage 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.  \nKeywords: immunohistochemical staining; human leukocyte antigen class I; cancer vaccine; chimeric antigen receptor-T (CAR-T) cell therapy; T cell receptor-T (TCR-T) cell therapy  \n1. Introduction  \nColorectal cancer (CRC) is one of the most common cancers with a rising global incidence rate [1–4] . Recent advancements in immunotherapy, including immune checkpoint inhibitors, offer promising strategies t","cbCaicv20K0pEI77","https://ap.wps.com/l/cbCaicv20K0pEI77","pdf",9009433,"English","# Abstract\n# Keywords\n# 1. Introduction\n## Colorectal cancer burden and treatment limitations\n## Immunotherapy approaches and rationale","[{\"question\":\"What was the main goal of the study?\",\"answer\":\"To identify common cancer antigens using immunohistochemical staining as promising targets for antigen-specific immunotherapies in colorectal cancer and liver metastases.\"},{\"question\":\"Which antigens and markers were evaluated in the specimens?\",\"answer\":\"Seven cancer antigens (CLDN1, EphB4, LAT1, FOXM1, HSP105α, ROBO1, SPARC) and HLA class I were assessed for expression and localization.\"},{\"question\":\"How did antigen expression differ between primary tumors and liver metastases?\",\"answer\":\"In primaries, most antigens were expressed in the majority of cases, while in liver metastases FOXM1 and SPARC showed reduced expression compared with primaries; other antigens and HLA class I were highly expressed in both.\"}]","Identification of Common Cancer Antigens Useful for Specific Immunotherapies to Colorectal Cancer and Liver Metastases | PDF",1790192771,48]