Altered HLA Class I and HLA-G Expression Is Associated with IL-10 Expression in Patients with Cervical Cancer

Rodríguez, Josefa Antonia; Galeano, Laila; Palacios, Diana; Gómez, Constanza; López, M. L. Vidal; Bravo, María Mercedes; Cómbita, Alba Lucía

doi:10.1159/000334089

Cited by 55 publications

(52 citation statements)

References 125 publications

(86 reference statements)

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“…In previous studies, HLA-G expression was found in 27–30 % of the primary- [28, 55] and 11 % of the metastatic tumor samples [28], but without histological subtyping. Here, comparable results were obtained with approximately 25 % of the cases having expression of HLA-G in the primary tumor and 11 % in the metastatic LNs.…”

Section: Discussionmentioning

confidence: 99%

Classical and non-classical HLA class I aberrations in primary cervical squamous- and adenocarcinomas and paired lymph node metastases

Ferns¹,

Heeren²,

Samuels³

et al. 2016

j. immunotherapy cancer

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BackgroundTumors 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.MethodsClassical (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 Chi2 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.ResultsDecreased 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).ConclusionThese 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s40425-016-0184-3) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Classical and non-classical HLA class I aberrations in primary cervical squamous- and adenocarcinomas and paired lymph node metastases

Ferns¹,

Heeren²,

Samuels³

et al. 2016

j. immunotherapy cancer

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“…These studies showed that HLA-G expression is negative in normal cervical tissues. Though no normal cervical tissues were included, Rodríguez et al [29] found that HLA-G protein expression (mAb 4H84) was observed in 27.6% (16/58) of cases. To the contrary, a study by Zhou et al [30] addressed that a strong and uniform HLA-G expression (mAb MEM-G/1) in normal epithelium, while only a small proportion of CINs and cervical squamous cell carcinoma samples showed reduced expression of HLA-G.…”

Section: Discussionmentioning

confidence: 99%

Human leukocyte antigen-G (HLA-G) expression in cervical cancer lesions is associated with disease progression

Zhang²,

Lin³

et al. 2012

Human Immunology

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“…IL-10 contributes to the impairment of the anti-tumor immune response, either by downregulating human leukocyte antigen Class I expression or by increasing HLA-G expression in human trophoblasts and monocytes (46,47) and certain cancer models, such as lung cancer (48). HLA-G is known to inhibit the cytotoxic activity of T lymphocytes and natural killer (NK) cells (49,50), which is associated with cancer development and immune tolerance.…”

Section: Il-10 Exerts a Tumor-promoting Effect In Cervical Cancermentioning

confidence: 99%

The paradox of IL-10-mediated modulation in cervical cancer

Wang

Liu

et al. 2013

Biomedical Reports

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Abstract. Interleukin-10 (IL-10) has opposing effects as an anti-inflammatory (potentially cancer-promoting) and antiangiogenic (potentially cancer-inhibiting) agent. The role of IL-10 in cervical cancer is also dual. Here, we review the IL-10-mediated tumor-promoting effect and tumor-inhibiting effects in cervical cancer, among which, human papilloma virus (HPV), human leukocyte antigen-G (HLA-G) and IL-10 polymorphisms are associated with the development of cervical cancer. IL-10 is also used for the therapy of cervical cancer through enhancing proliferation, expression of immunologically important surface molecules and increasing Th1 cytokine production and cytotoxic potential in HPV-specific CD8 (+) cytotoxic T lymphocytes.

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Altered HLA Class I and HLA-G Expression Is Associated with IL-10 Expression in Patients with Cervical Cancer

Cited by 55 publications

References 125 publications

Classical and non-classical HLA class I aberrations in primary cervical squamous- and adenocarcinomas and paired lymph node metastases

Classical and non-classical HLA class I aberrations in primary cervical squamous- and adenocarcinomas and paired lymph node metastases

Human leukocyte antigen-G (HLA-G) expression in cervical cancer lesions is associated with disease progression

The paradox of IL-10-mediated modulation in cervical cancer

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