Identification of Common Cancer Antigens Useful for Specific Immunotherapies to Colorectal Cancer and Liver Metastases
Abstract
1. Introduction
2. Results
2.1. Expression of Seven Common Cancer Antigens and HLA Class I on Cell Membrane in 25 Cases of Primary CRC
2.2. Expression of Seven Common Cancer Antigens and HLA Class I on Cell Membrane in 60 Cases of CRC Liver Metastases
2.3. Expression of Seven Common Cancer Antigens and HLA Class I on Cell Membrane in 14 Cases of Primary CRCLM
2.4. The Development of a Multiplex Fluorescence Immunohistochemical Staining System for Common Cancer Antigens and HLA Class I Detection
3. Discussion
4. Materials and Methods
4.1. Clinical Samples
4.2. Immunohistochemical Analysis of Common Cancer Antigens and HLA Class I
4.3. Multiplex Fluorescence Immunohistochemical Staining and Analysis of Cancer Antigens and HLA Class I
4.4. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
CAF | Cancer-associated fibroblast |
CAR-T | Chimeric antigen receptor-T |
CLDN1 | Claudin 1 |
CRCLM | Colorectal cancer liver metastases |
EphB4 | Ephrin type-B receptor 4 |
FOXM1 | Forkhead box M1 |
HLA | Human leukocyte antigen |
HSP105α | Heat shock protein 105α |
IHC | Immunohistochemical staining |
LAT1 | L-type amino acid transporter 1 |
MFIH | Multiplex fluorescence immunohistochemistry |
MMR | Mismatch repair |
NCCN | National Comprehensive Cancer Network |
ROBO1 | Roundabout homolog-1 |
ROI | Region of interest |
SPARC | Secreted protein acidic and rich in cysteine |
TCR-T | T cell receptor-T |
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Primary Colorectal Cancer | ||||||||
---|---|---|---|---|---|---|---|---|
Cancer Antigens * | CLDN1 | EphB4 | LAT1 | FOXM1 | HSP105α | ROBO1 | SPARC | HLA class I |
Score: Median [range] | ||||||||
All cases (n = 25) | 5.3 [0–6.0] | 5.0 [0–6.0] | 5.3 [0.7–6.0] | 5.0 [0–6.0] | 6.0 [3.0–6.0] | 4.7 [0.7–6.0] | 5.7 [1.7–6.0] | 4.7 [0–5.3] |
Cases of expression > 3 | ||||||||
All cases (n = 25) | 23 (92.0%) | 24 (96.0%) | 24 (96.0%) | 22 (88.0%) | 24 (96.0%) | 23 (92.0%) | 24 (96.0%) | 20 (80.0%) |
Colorectal cancer liver metastases | ||||||||
Cancer Antigens * | CLDN1 | EphB4 | LAT1 | FOXM1 | HSP105α | ROBO1 | SPARC | HLA class I |
Score: Median [range] | ||||||||
All cases (n = 60) | 4.3 [0–6.0] | 4.3 [0–6.0] | 3.7 [0–6.0] | 2.7 [0–6.0] | 5.0 [0–6.0] | 4.0 [0–6.0] | 2.7 [0–5.0] | 3.7 [0–6.0] |
Naïve (n = 12) | 4.3 [3.3–6.0] | 5.0 [0–6.0] | 3.7 [1.3–5.7] | 2.5 [0–5.0] | 4.7 [3.3–6.0] | 4.2 [0–6.0] | 2.3 [1.0–5.0] | 3.7 [0–5.0] |
Chemotherapy (n = 48) | 4.3 [0–6.0] | 4.0 [0–6.0] | 3.7 [0–6.0] | 2.7 [0–6.0] | 5.0 [0–6.0] | 3.7 [0–6.0] | 2.7 [1.0–4.0] | 3.7 [0–6.0] |
Cases of expression > 3 | ||||||||
All cases (n = 60) | 53 (88.3%) | 44 (76.6%) | 36 (60.0%) | 23 (38.3%) | 57 (95.0%) | 38 (63.3%) | 20 (33.3%) | 37 (61.7%) |
Naïve (n = 12) | 12 (100.0%) | 8 (66.7%) | 7 (58.3%) | 2 (16.7%) | 12 (100.0%) | 8 (66.7%) | 2 (16.7%) | 10 (83.3%) |
Chemotherapy (n = 48) | 41 (85.4%) | 36 (75.0%) | 29 (60.4%) | 21 (43.8%) | 45 (93.8%) | 30 (62.5%) | 18 (37.5%) | 27 (56.2%) |
Primary Colorectal Cancer | ||||||||
---|---|---|---|---|---|---|---|---|
Cancer Antigens * | CLDN1 | EphB4 | LAT1 | FOXM1 | HSP105α | ROBO1 | SPARC | HLA class I |
Score: Median [range] | ||||||||
All cases (n = 14) | 5.7 [0–6.0] | 5.0 [0–6.0] | 5.3 [3.0–6.0] | 4.5 [2.7–6.0] | 5.0 [0–6.0] | 5.0 [0.7–6.0] | 5.7 [1.7–6.0] | 4.0 [0–5.3] |
Naïve (n = 11) | 5.7 [0–6.0] | 5.0 [5.0–6.0] | 5.3 [3.0–6.0] | 4.7 [2.7–6.0] | 5.0 [0–6.0] | 4.7 [0.7–6.0] | 5.7 [1.7–6.0] | 4.0 [0–5.3] |
Chemotherapy (n = 3) | 5.7 [4.0–6.0] | 4.3 [2.3–6.0] | 5.3 [5.0–5.7] | 4.3 [3.0–4.7] | 5.20 [4.3–6.0] | 5.0 [5.0–6.0] | 6.0 [5.0–6.0] | 3.3 [1.3–5.3] |
Cases of expression > 3 | ||||||||
All cases (n = 14) | 13 (92.9%) | 12 (85.7%) | 13 (92.9%) | 11 (78.6%) | 13 (92.9%) | 12 (85.7%) | 13 (92.9%) | 9 (64.2%) |
Naïve (n = 11) | 10 (90.9%) | 10 (90.9%) | 10 (90.9%) | 9 (81.8%) | 10 (90.9%) | 9 (81.8%) | 10 (90.9%) | 7 (63.6%) |
Chemotherapy (n = 3) | 3 (100.0%) | 2 (66.7%) | 3 (100.0%) | 2 (66.7%) | 3 (100.0%) | 3 (100.0%) | 3 (100.0%) | 2 (66.7%) |
Colorectal cancer liver metastases | ||||||||
Cancer Antigens * | CLDN1 | EphB4 | LAT1 | FOXM1 | HSP105α | ROBO1 | SPARC | HLA class I |
Score: Median [range] | ||||||||
All cases (n = 14) | 5.5 [1.7–6.0] | 4.3 [0–6.0] | 5.2 [0–6.0] | 2.3 [0–3.3] | 5.0 [3.3–6.0] | 5.0 [4.0–6.0] | 2.7 [0–5.0] | 5.0 [1.7–6.0] |
Naïve (n = 5) | 5.0 [1.7–5.7] | 5.0 [2.3–5.3] | 5.0 [0.3–6.0] | 3.0 [2.3–3.3] | 5.3 [4.7–5.7] | 5.0 [4.0–5.7] | 0.0 [0–5.0] | 5.0 [1.7–5.7] |
Chemotherapy (n = 9) | 5.0 [1.7–6.0] | 4.0 [0–6.0] | 5.3 [0–6.0] | 1.3 [0.3–3.3] | 5.0 [3.3–6.0] | 5.0 [2.7–6.0] | 2.7 [0–4.3] | 5.0 [2.7–5.7] |
Cases of expression > 3 | ||||||||
All cases (n = 14) | 13 (92.9%) | 9 (64.2%) | 11 (78.6%) | 4 (28.6%) | 14 (100.0%) | 12 (85.7%) | 5 (35.7%) | 11 (78.6%) |
Naïve (n = 5) | 5 (100.0%) | 3 (60.0%) | 3 (60.0%) | 3 (60.0%) | 5 (100.0%) | 4 (80.0%) | 2 (40.0%) | 4 (80.0%) |
Chemotherapy (n = 9) | 8 (88.9%) | 6 (66.7%) | 8 (88.9%) | 1 (11.1%) | 9 (100.0%) | 8 (88.9%) | 3 (33.3%) | 7 (77.8%) |
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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://doi.org/10.3390/ijms26157402
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. International Journal of Molecular Sciences. 2025; 26(15):7402. https://doi.org/10.3390/ijms26157402
Chicago/Turabian StyleKataoka, Jun, Kazumasa Takenouchi, Toshihiro Suzuki, Kazunobu Ohnuki, Yuichiro Tsukada, Naoto Gotohda, Masaaki Ito, and Tetsuya Nakatsura. 2025. "Identification of Common Cancer Antigens Useful for Specific Immunotherapies to Colorectal Cancer and Liver Metastases" International Journal of Molecular Sciences 26, no. 15: 7402. https://doi.org/10.3390/ijms26157402
APA StyleKataoka, J., Takenouchi, K., Suzuki, T., Ohnuki, K., Tsukada, Y., Gotohda, N., Ito, M., & Nakatsura, T. (2025). Identification of Common Cancer Antigens Useful for Specific Immunotherapies to Colorectal Cancer and Liver Metastases. International Journal of Molecular Sciences, 26(15), 7402. https://doi.org/10.3390/ijms26157402