Differential role of HLA-A and HLA-B, C expression levels as prognostic markers in colon and rectal cancer
Purpose The association of human leucocyte antigen (HLA) class I expression levels with the clinical course of many malignancies reflects their crucial role in the recognition and elimination of malignant cells by cognate T cells and NK cells. In colorectal cancer, results regarding this association...
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| Language: | English |
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BMJ Publishing Group
2022-03-01
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| Series: | Journal for ImmunoTherapy of Cancer |
| Online Access: | https://jitc.bmj.com/content/10/3/e004115.full |
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| author | Wilko Weichert Lei Cai Soldano Ferrone Peter J K Kuppen Lindy G Durrant Theodoros Michelakos Filippos Kontos Tomohiro Kurokawa Ananthan Sadagopan Danielle Krijgsman Cristina R Ferrone |
| author_facet | Wilko Weichert Lei Cai Soldano Ferrone Peter J K Kuppen Lindy G Durrant Theodoros Michelakos Filippos Kontos Tomohiro Kurokawa Ananthan Sadagopan Danielle Krijgsman Cristina R Ferrone |
| author_sort | Wilko Weichert |
| collection | DOAJ |
| description | Purpose The association of human leucocyte antigen (HLA) class I expression levels with the clinical course of many malignancies reflects their crucial role in the recognition and elimination of malignant cells by cognate T cells and NK cells. In colorectal cancer, results regarding this association are conflicting. The potential pathogenetic and therapeutic implications of this association prompted us to perform a large patient-level pooled analysis assessing the role of the expression level of HLA class I loci gene products in colon and rectal cancer.Experimental design Included studies provided patient-level data on HLA class I expression levels determined by immunohistochemistry on surgical specimens. Expression levels of the HLA class I loci gene products (HLA-A, HLA-B/C) were correlated with common genetic events and survival.Results Data from 5 studies including 2863 patients were used. In the 1620 colon cancer patients, lower HLA-A, HLA-B/C and total HLA class I expression levels were associated with microsatellite instability (p=0.044, p=0.008 and p=0.022, respectively), higher frequency of BRAF mutations (p<0.001, p=0.021 and p<0.001, respectively) and lower frequency of KRAS mutations (p=0.001, ns and p=0.002, respectively). In the 1243 rectal cancer patients, HLA-A expression was higher in tumors treated with neoadjuvant radiation (p=0.024). High HLA-B/C, but not HLA-A, expression level was an independent predictor of favorable overall survival in colon (p=0.006) and rectal (p<0.001) cancer.Conclusions T-cells and HLA-B/C antigens, rather than NK cells and HLA-A antigens, likely play an important role in controlling colon/rectal cancer growth. Colon/rectal cancer patients may benefit from strategies that upregulate HLA-B/C and trigger or enhance T cell immunity. |
| format | Article |
| id | doaj-art-e7b9bb0a184e4674bba2e19cb5b513a1 |
| institution | DOAJ |
| issn | 2051-1426 |
| language | English |
| publishDate | 2022-03-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | Journal for ImmunoTherapy of Cancer |
| spelling | doaj-art-e7b9bb0a184e4674bba2e19cb5b513a12025-08-20T03:05:14ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262022-03-0110310.1136/jitc-2021-004115Differential role of HLA-A and HLA-B, C expression levels as prognostic markers in colon and rectal cancerWilko Weichert0Lei Cai1Soldano Ferrone2Peter J K Kuppen3Lindy G Durrant4Theodoros Michelakos5Filippos Kontos6Tomohiro Kurokawa7Ananthan Sadagopan8Danielle Krijgsman9Cristina R Ferrone106 Institute of Pathology, Technical University Munich, München, GermanyDepartment of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USADepartment of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USADepartment of Surgery, Leiden University Medical Center, Leiden, The NetherlandsBiodiscovery Institute, University of Nottingham Faculty of Medicine and Health Sciences, Nottingham, UKDepartment of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USADepartment of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USADepartment of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USADepartment of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USADepartment of Surgery, Leiden University Medical Center, Leiden, The NetherlandsDepartment of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USAPurpose The association of human leucocyte antigen (HLA) class I expression levels with the clinical course of many malignancies reflects their crucial role in the recognition and elimination of malignant cells by cognate T cells and NK cells. In colorectal cancer, results regarding this association are conflicting. The potential pathogenetic and therapeutic implications of this association prompted us to perform a large patient-level pooled analysis assessing the role of the expression level of HLA class I loci gene products in colon and rectal cancer.Experimental design Included studies provided patient-level data on HLA class I expression levels determined by immunohistochemistry on surgical specimens. Expression levels of the HLA class I loci gene products (HLA-A, HLA-B/C) were correlated with common genetic events and survival.Results Data from 5 studies including 2863 patients were used. In the 1620 colon cancer patients, lower HLA-A, HLA-B/C and total HLA class I expression levels were associated with microsatellite instability (p=0.044, p=0.008 and p=0.022, respectively), higher frequency of BRAF mutations (p<0.001, p=0.021 and p<0.001, respectively) and lower frequency of KRAS mutations (p=0.001, ns and p=0.002, respectively). In the 1243 rectal cancer patients, HLA-A expression was higher in tumors treated with neoadjuvant radiation (p=0.024). High HLA-B/C, but not HLA-A, expression level was an independent predictor of favorable overall survival in colon (p=0.006) and rectal (p<0.001) cancer.Conclusions T-cells and HLA-B/C antigens, rather than NK cells and HLA-A antigens, likely play an important role in controlling colon/rectal cancer growth. Colon/rectal cancer patients may benefit from strategies that upregulate HLA-B/C and trigger or enhance T cell immunity.https://jitc.bmj.com/content/10/3/e004115.full |
| spellingShingle | Wilko Weichert Lei Cai Soldano Ferrone Peter J K Kuppen Lindy G Durrant Theodoros Michelakos Filippos Kontos Tomohiro Kurokawa Ananthan Sadagopan Danielle Krijgsman Cristina R Ferrone Differential role of HLA-A and HLA-B, C expression levels as prognostic markers in colon and rectal cancer Journal for ImmunoTherapy of Cancer |
| title | Differential role of HLA-A and HLA-B, C expression levels as prognostic markers in colon and rectal cancer |
| title_full | Differential role of HLA-A and HLA-B, C expression levels as prognostic markers in colon and rectal cancer |
| title_fullStr | Differential role of HLA-A and HLA-B, C expression levels as prognostic markers in colon and rectal cancer |
| title_full_unstemmed | Differential role of HLA-A and HLA-B, C expression levels as prognostic markers in colon and rectal cancer |
| title_short | Differential role of HLA-A and HLA-B, C expression levels as prognostic markers in colon and rectal cancer |
| title_sort | differential role of hla a and hla b c expression levels as prognostic markers in colon and rectal cancer |
| url | https://jitc.bmj.com/content/10/3/e004115.full |
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