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

TL;DR

This study identifies cancer antigens in colorectal cancer and liver metastases that could be targeted for immunotherapies.

Contribution

The study identifies specific cancer antigens and HLA class I expression patterns for immunotherapy targeting in colorectal cancer and liver metastases.

Findings

CLDN1, EphB4, and LAT1 are highly expressed in both colorectal cancer and liver metastases.

HLA class I is expressed on the cell membrane in 80% of primary tumors.

FOXM1 and SPARC expression is lower in liver metastases compared to primary tumors.

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.

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