FoxP3+ and IL-17+ cells are correlated with improved prognosis in cervical adenocarcinoma

Punt, Simone; Vliet, Marjolein E. van; Spaans, Vivian M.; Kroon, Cornelis D. de; Fleuren, Gert Jan; Gorter, Arko; Jordanova, Ekaterina S.

doi:10.1007/s00262-015-1678-4

Cited by 53 publications

(57 citation statements)

References 46 publications

(48 reference statements)

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“…In contrast, we found EGFR upregulation exclusively in SCC [68]. Currently, we are focusing on understanding the immunological differences between SCC and AC, and we are investigating the presence of different immune cell subsets which may give us more information on the different role of HLA expression in these histological subtypes [32–36]. In addition, there was more complete HLA-A loss in SCC metastasis, while there was more complete loss of HLA-B/C in AC metastasis, again emphasizing the need for better immune-characterization of the two major cervical cancer histological subtypes.…”

Section: Resultsmentioning

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: Resultsmentioning

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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“…For the detection and the characterisation of tumour-infiltrating T cells, we used a triple immunofluorescent staining, as previously described [15]. After antigen retrieval using Tris–EDTA buffer pH 9.0, whole sections were incubated overnight at 4 °C with the combination of primary antibodies, as detailed in Table 2.…”

Section: Methodsmentioning

confidence: 99%

Increased PD-L1 and T-cell infiltration in the presence of HLA class I expression in metastatic high-grade osteosarcoma: a rationale for T-cell-based immunotherapy

Sundara

Kostine

Cleven

et al. 2016

Cancer Immunol Immunother

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IntroductionImmunotherapy may be an excellent choice for treating osteosarcoma given its exceptionally high genomic instability, potentially generating neoantigens. In this study, we aim to investigate the HLA class I expression, PD-L1 and tumour-infiltrating lymphocytes in primary osteosarcomas and relapses/metastases, as well as their changes during disease progression.Materials and methodsTumour samples from multiple stages of the disease (pretreatment biopsies, surgical resections of primary osteosarcomas, relapses and metastases) were collected and stained for HLA-A (HCA2), HLA-B/C (HC10), β2-microglobulin and PD-L1 using immunohistochemistry on whole sections. Density and type of T-cell infiltrate were characterised by a triple immunofluorescent staining CD3-CD8-FOXP3.ResultsOverall, 85 formalin-fixed, paraffin-embedded blocks from 25 osteosarcoma patients were included. HLA class I expression was detected in 94% of osteosarcomas (strongly positive in 56%, heterogeneous in 38%) and negative or weakly positive in 6%, without differences between the stages of the disease. HLA-A expression was more frequently negative than HLA-B/C. Tumour-infiltrating lymphocytes were highly heterogeneous and mainly observed in tumour areas with expression of HLA class I. Density of T cells was significantly higher in metastases than in primary tumours and local relapses (p = 0.0003). Positive PD-L1 expression was found in 13% of primary tumours, 25% of relapses and 48% of metastases and correlated with a high T-cell infiltrate (p = 0.002).ConclusionAn increased number of tumour-infiltrating T cells and PD-L1 expression in metastases compared with primary tumours, suggesting accessibility for T cells, could imply that osteosarcoma patients with metastatic disease may benefit from T-cell-based immunotherapy.Electronic supplementary materialThe online version of this article (doi:10.1007/s00262-016-1925-3) contains supplementary material, which is available to authorized users.

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“…A recent phenotypic analysis of T H 17 cells revealed that they resembled terminally differentiated memory T-cells, and strongly promoted long-term anti-tumor immunity [29]. Increased T H 17 population was associated with a better prognosis in patients with cervical adenocarcinoma [30]. A cytokine macrophage inhibitory factor (MIF) that strongly promoted the generation of T H 17 was significantly associated with a better survival in patients with nasopharyngeal carcinomas [31].…”

Section: Does the Number Of T-cells In The Tumor Microenvironment Matmentioning

confidence: 99%

Telltale tumor infiltrating lymphocytes (TIL) in oral, head & neck cancer

et al. 2016

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Evidence gleaned from recent studies on the role of tumor-infiltrating lymphocytes (TILs) suggests that cancer is not only a genetic disease but also an immunologic disease. Head and Neck Squamous Cell Carcinoma (HNSCC) has been a significant model to study cancer cell-immune cell interactions. First, immune cell infiltration is an important feature of these tumors. Second, HNSCC frequently develops resistance to immunogenic cytotoxicity, which provides a window to decipher how tumors engage the immune system to establish immune tolerance. Finally, chemoradiation therapy, as a central modality for HNSCC treatment, has been shown to elicit immune activation. The presence of effector immune cells in the tumor microenvironment is often associated with superior clinical response to adjuvant therapy. On the other hand, an activated immune system, in addition to limiting tumor initiation and progression, could also exert selective pressure to promote the growth of less immunogenic tumors, as a pivotal immunoediting process. But it remains unclear how cancer cell signaling regulates tumor immunogenicity and how to mitigate HNSCC-potentiated TIL suppression. In this review, we will revisit the prognostic role of TILs in HNSCC, and collectively discuss how cancer cell machinery impacts upon the plasticity of TILs.

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FoxP3+ and IL-17+ cells are correlated with improved prognosis in cervical adenocarcinoma

Cited by 53 publications

References 46 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

Increased PD-L1 and T-cell infiltration in the presence of HLA class I expression in metastatic high-grade osteosarcoma: a rationale for T-cell-based immunotherapy

Telltale tumor infiltrating lymphocytes (TIL) in oral, head & neck cancer

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