Identification of Common Cancer Antigens Useful for Specific Immunotherapies to Colorectal Cancer and Liver Metastases

Sep 23, 2026

Stage IV colorectal cancer has poor outcomes and liver metastases frequently recur even after resection. This study used immunohistochemical staining to identify common cancer antigens as targets for antigen-specific immunotherapies in colorectal cancer and liver metastases. Expression levels and intracellular localization of seven antigens (CLDN1, EphB4, LAT1, FOXM1, HSP105α, ROBO1, SPARC) and HLA class I were assessed in 85 surgical specimens, including primaries and liver metastases.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages19

Reading Time48 min

AccessFree to download

Abstract

Keywords

1. Introduction

Colorectal cancer burden and treatment limitations

Immunotherapy approaches and rationale

Article Identification of Common Cancer Antigens Useful for Specific Immunotherapies to Colorectal Cancer and Liver Metastases Jun Kataoka 1,2,3, Kazumasa Takenouchi 1, Toshihiro Suzuki 1, Kazunobu Ohnuki 1, Yuichiro Tsukada 2, Naoto Gotohda 3,4, Masaaki Ito 2 and Tetsuya Nakatsura 1, * Academic Editors: Karolina Orywaland Mariusz Gryko Received: 9 June 2025 Revised: 23 July 2025 Accepted: 24 July 2025 Published: 31 July 2025 Citation: Kataoka, J.; 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) [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/)) . 1 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.) 2 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.) 3 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) 4 Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa 277-8577, Japan * Correspondence: [tnakatsu@east.ncc.go.jp](tnakatsu@east.ncc.go.jp); Tel.: +81-4-7131-5490 Abstract 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. Keywords: 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 1. Introduction Colorectal 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

FAQs

What was the main goal of the study?

To identify common cancer antigens using immunohistochemical staining as promising targets for antigen-specific immunotherapies in colorectal cancer and liver metastases.

Which antigens and markers were evaluated in the specimens?

Seven cancer antigens (CLDN1, EphB4, LAT1, FOXM1, HSP105α, ROBO1, SPARC) and HLA class I were assessed for expression and localization.

How did antigen expression differ between primary tumors and liver metastases?

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.

Sep 23, 2026

Uploaded by supergirl