Characterising the prognostic potential of HLA-DR during colorectal cancer development
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2020Access:
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Dunne M.R., Phelan J.J., Michielsen A.J., Maguire A.A., Dunne C., Martin P., Noonan S., Tosetto M., Geraghty R., Fennelly D., Sheahan K., Ryan E.J., O'Sullivan J., Characterising the prognostic potential of HLA-DR during colorectal cancer development., Cancer Immunology Immunotherapy, 2020 Aug;69(8):1577-1588Abstract:
HLA-DR, an MHC class II molecule that mediates antigen presentation, is a favourable prognostic indicator in colorectal cancer (CRC). However, the dynamics and location of HLA-DR expression during CRC development are unclear. We aimed to define HLA-DR expression by immunohistochemistry in colorectal epithelium and stromal tissue at different stages of cancer development, assessing non-neoplastic colorectal adenocarcinoma–adjacent tissue, adenomas and carcinoma tissues, and to associate HLA-DR levels with clinical outcomes. Patients with higher than median HLA-DR expression survived at least twice as long as patients with lower expression. This association was significant for HLA-DR staining in the colorectal carcinoma epithelium (n = 152, p = 0.011, HR 1.9, 95% CI 1.15–3.15) and adjacent non-neoplastic epithelium (n = 152, p < 0.001, HR 2.7, 95% CI 1.59–4.66), but not stroma. In stage II cases, however, the prognostic value of HLA-DR expression was significant only in adjacent non-neoplastic tissues, for both epithelium (n = 63, p = 0.015, HR 3.6, 95% CI 1.279–10.25) and stroma (n = 63, p = 0.018, HR 5.07, 95% CI 1.32–19.49). HLA-DR was lower in carcinoma tissue compared to matched adenomas (n = 35), in epithelium (p < 0.01) and stroma (p < 0.001). HLA-DR was further reduced in late-stage carcinoma (n = 101) compared to early stage (n = 105), in epithelium (p < 0.001) and stroma (p < 0.01). HLA-DR expression was lower (p < 0.05) in the adjacent non-neoplastic epithelium of patients with cancer recurrence. We demonstrate a progressive loss of HLA-DR in epithelial and stromal tissue compartments during CRC development and show prognostic ability in carcinoma–adjacent non-neoplastic tissues, highlighting the importance of this molecule in the anti-cancer immune response. These findings may have wider implications for immunotherapeutic interventions.
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http://people.tcd.ie/phelanj3http://people.tcd.ie/dunnem12
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Author: Phelan, James; Dunne, Margaret
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Cancer Immunology Immunotherapy;Availability:
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immunotherapeutic interventions., HLA-DR, an MHC class II molecule, colorectal cancer (CRC), Adenoma, Cancer immunology, Cancer recurrence, Colorectal cancer, HLA-DR, Prognostic biomarkersSubject (TCD):
CancerDOI:
http://dx.doi.org/10.1007/s00262-020-02571-2Metadata
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