Title |
Classical and non-classical HLA class I aberrations in primary cervical squamous- and adenocarcinomas and paired lymph node metastases
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Published in |
Journal for Immunotherapy of Cancer, November 2016
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DOI | 10.1186/s40425-016-0184-3 |
Pubmed ID | |
Authors |
Debbie M. Ferns, A. Marijne Heeren, Sanne Samuels, Maaike C. G. Bleeker, Tanja D. de Gruijl, Gemma G. Kenter, Ekaterina S. Jordanova |
Abstract |
Tumors avoid destruction by cytotoxic T cells (CTL) and natural killer (NK) cells by downregulation of classical human leukocyte antigens (HLA) and overexpression of non-classical HLA. This is the first study to investigate HLA expression in relation to histology (squamous cell carcinoma (SCC) vs. adenocarcinoma (AC)), clinicopathological parameters and survival in a large cervical cancer patient cohort. Classical (HLA-A and HLA-B/C)- and non-classical HLA molecules (HLA-E and HLA-G) were studied on primary tumors and paired lymph node (LN) metastases from cervical cancer patients (n = 136) by immunohistochemistry. The Chi(2) test was used for the comparison of clinicopathological characteristics between SCC and AC patients. The Related-Samples Wilcoxon Signed Rank test was used to compare HLA expression between the primary tumor and metastasis in LN. Patient survival rates were analyzed by Kaplan-Meier curves and Log Rank test. The Mann-Whitney U Test was used to compare the distribution of HLA class I expression between SCC and AC. Decreased expression of HLA-A (SCC P < 0.001), HLA-B/C (SCC P < 0.01; AC P < 0.01) and total classical HLA (SCC P < 0.001; AC P = 0.02) was apparent in metastatic tumor cells compared to the primary tumor. In primary SCC, there was a clear trend towards complete loss of HLA-A (P = 0.05). SCC metastases showed more complete loss of HLA-A, while AC metastases showed more complete loss of HLA-B/C (P = 0.04). In addition, tumor size and parametrium involvement were also related to aberrant HLA class I expression. No significant associations between HLA expression and disease-specific (DSS) or disease-free survival (DFS) were found in this advanced disease cohort. However, in the SCC group, samples showing loss of HLA-A or loss of total classical HLA but positive for HLA-G were linked to poor patient survival (DSS P = 0.001 and P = 0.01; DFS P = 0.003 and P = 0.01, for HLA-A and total classical HLA, respectively). These results strengthen the idea of tumor immune escape variants leading to metastasis. Moreover, SCC tumors showing downregulation of HLA-A or total classical HLA in combination with HLA-G expression had poor prognosis. Our findings warrant further analysis of HLA expression as a biomarker for patient selection for CTL- and NK- cell based immunotherapeutic intervention. |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Portugal | 1 | 2% |
Unknown | 54 | 98% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Master | 10 | 18% |
Student > Ph. D. Student | 10 | 18% |
Researcher | 6 | 11% |
Student > Doctoral Student | 5 | 9% |
Other | 4 | 7% |
Other | 10 | 18% |
Unknown | 10 | 18% |
Readers by discipline | Count | As % |
---|---|---|
Biochemistry, Genetics and Molecular Biology | 13 | 24% |
Medicine and Dentistry | 13 | 24% |
Immunology and Microbiology | 9 | 16% |
Agricultural and Biological Sciences | 4 | 7% |
Social Sciences | 1 | 2% |
Other | 1 | 2% |
Unknown | 14 | 25% |