Down-regulation of Human Leukocyte Antigen class I heavy chain in tumors is associated with a poor prognosis in advanced esophageal cancer patients

Tanaka, Kimitaka; Tsuchikawa, Takahiro; Miyamoto, Masaki; Maki, Takehiro; Ichinokawa, Masaomi; Kubota, Kanako; Shichinohe, Toshiaki; Hirano, Satoshi; Ferrone, Soldano; Dosaka‐Akita, Hirotoshi; Matsuno, Yoshihiro; Kondo, Satoshi

doi:10.3892/ijo.2011.1274

Cited by 42 publications

(37 citation statements)

References 29 publications

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“…TMAs were constructed as described in our previous report (24). Patients without information about survival or broken and poor samples were omitted from analysis.…”

Section: Human Pdac Tissue Samplesmentioning

confidence: 99%

Chemotherapy-Derived Inflammatory Responses Accelerate the Formation of Immunosuppressive Myeloid Cells in the Tissue Microenvironment of Human Pancreatic Cancer

et al. 2015

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“…TMAs were constructed as described in our previous report (24). Patients without information about survival or broken and poor samples were omitted from analysis.…”

Section: Human Pdac Tissue Samplesmentioning

confidence: 99%

Chemotherapy-Derived Inflammatory Responses Accelerate the Formation of Immunosuppressive Myeloid Cells in the Tissue Microenvironment of Human Pancreatic Cancer

et al. 2015

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“…However, we observed that the percentage of CD8 + T cells exhibited a consistently positive correlation with the expression of TAP-1, TAP-2 and HLA-I, whereas the expression of IL-10 had a negative correlation with the expression of TAP-1, TAP-2 and HLA-I in NPC. These results suggest that the reduction in the expression of TAP-1, TAP-2 and HLA-I may contribute to the immunosuppression associated with in NPC, which may help tumor cells escape immune surveillance (20).…”

Section: Discussionmentioning

confidence: 85%

Downregulation of expression of transporters associated with antigen processing 1 and 2 and human leukocyte antigen I and its effect on immunity in nasopharyngeal carcinoma patients

Ren

Yang

Zhang

et al. 2013

Molecular and Clinical Oncology

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Abstract. The human leukocyte antigen (HLA)-I and antigen-processing machinery (APM) are crucial in the anticancer immune response. The aim of this study was to assess the clinical significance of the APM components [transporters associated with antigen processing (TAP)-1 and -2 and HLA-I] in nasopharyngeal carcinoma (NPC). A total of 58 NPC specimens and 20 healthy specimens used as control were evaluated by semiquantitative immunohistochemistry for three APM components (TAP-1, TAP-2 and HLA-I). The expression of the APM components in NPC was downregulated. CD4 + and CD8 + T cells were measured by flow cytometry and IL-10 was measured by ELISA. The number of CD8 + T cells and the expression of IL-10 were higher and the number of CD4 + T cells was lower in NPC, compared to the controls. The number of CD8 + T cells and the expression of IL-10 were negatively correlated with TAP-1, TAP-2 and HLA-I expression. The clinical phase, lymph node metastasis, distant metastasis, pathological type, TAP-1 expression, TAP-2 expression and HLA-I expression were identified as prognostic factors by the Kaplan-Meier analysis. A multivariate analysis using a Cox regression model indicated that distant metastasis and the downregulation of HLA-Ⅰ expression were independent unfavorable prognostic factors. In conclusion, the lower expression of HLA-I induced immunosuppression in NPC patients and was associated with a poor prognosis. IntroductionViruses and tumors evade cytotoxic T lymphocyte-mediated host immunity through the downregulation of antigen-presentation machineries. This may be achieved by either the downregulation of transcription of antigen presentation genes, or the post-translational inactivation of the proteins involved in antigen presentation (1). The optimal cell surface expression of human leukocyte antigen (HLA) molecules requires the coordinated expression of several genes, such as transporters associated with antigen processing (TAP)-1 and -2, low molecular weight peptide (LMP)-2 and -7 and tapasin, as well as HLA class I heavy chain and β 2 -microglobulin (β 2 M). In cases of concurrent tumorigenesis and viral infection, the expression of these genes and the function of the encoded proteins are often impaired.Latent Epstein-Barr virus (EBV) infections are associated with lymphocyte and epithelial cell malignancies, with nasopharyngeal carcinoma (NPC) being the most frequent EBV-associated malignancy (2). The EBV-associated, undifferentiated form of NPC exhibits the most consistent association with EBV worldwide and is particularly common in China and Southeast Asia, reaching a peak incidence of ~20-30 cases per 100,000 individuals (3). In addition to genetic predisposition, EBV infection and environmental factors, such as dietary and geographic components, were considered to be important in the aetiology of NPC (4-6). Previous studies that used quantitative polymerase chain reaction to measure circulating tumor-derived EBV DNA in the blood of NPC patients demonstrated that the level of pre-treatment EBV DNA was...

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“…In terms of pancreatic cancer, Tewari et al[19] demonstrated a positive correlation between prognosis and the presence of tumor infiltrating T cells. Although the clinical relevance differs among types of cancer, in association with the HLA class I expression level[20], some agents have been reported to induce T-cell infiltration into pancreas cancers[21]. Homma et al[22] showed that CD4 + and CD8 + cells were significantly increased after neoadjuvant chemotherapy comprising gemcitabine and TS-1 followed by radiotherapy (NACRT), and a high accumulation of CD4 + cells offered a good prognostic marker for pancreas carcinoma after NACRT.…”

Section: Infiltrating T Lymphocytesmentioning

confidence: 99%

Clinical impact of chemotherapy to improve tumor microenvironment of pancreatic cancer

Tsuchikawa

Takeuchi

Nakamura

et al. 2016

WJGO

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A perioperative multimodal strategy including combination chemotherapy and radiotherapy, in addition to surgical resection, has been acknowledged to improve patient prognosis. However chemotherapy has not been actively applied as an immunomodulating modality because of concerns about various immunosuppressive effects. It has recently been shown that certain chemotherapeutic agents could modify tumor microenvironment and host immune responses through several underlying mechanisms such as immunogenic cell death, local T-cell infiltration and also the eradication of immune-suppressing regulatory cells such as regulatory T cells (Tregs) and myeloid-derived suppressor cells. With the better understanding of the cell components in the tumor microenvironment and the effect of chemotherapy to improve tumor microenvironment, it has been gradually clear that the chemotherapeutic agents is two-edged sword to have both immune promoting and suppressing effects. The cellular components of the tumor microenvironment include infiltrating T lymphocytes, dendritic cells, regulatory T cells, tumor associated macrophages, myeloid derived suppressor cells and cancer associated fibroblasts. Based on the better understanding of tumor microenvironment following chemotherapy, the treatment protocol could be modified as personalized medicine and the prognosis of pancreas cancer would be more improved utilizing multimodal chemotherapy. Here we review the recent advances of chemotherapy to improve tumor microenvironment of pancreatic cancer, introducing the unique feature of tumor microenvironment of pancreatic cancer, interaction between anti-cancer reagents and these constituting cells and future prospects.

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Down-regulation of Human Leukocyte Antigen class I heavy chain in tumors is associated with a poor prognosis in advanced esophageal cancer patients

Cited by 42 publications

References 29 publications

Chemotherapy-Derived Inflammatory Responses Accelerate the Formation of Immunosuppressive Myeloid Cells in the Tissue Microenvironment of Human Pancreatic Cancer

Chemotherapy-Derived Inflammatory Responses Accelerate the Formation of Immunosuppressive Myeloid Cells in the Tissue Microenvironment of Human Pancreatic Cancer

Downregulation of expression of transporters associated with antigen processing 1 and 2 and human leukocyte antigen I and its effect on immunity in nasopharyngeal carcinoma patients

Clinical impact of chemotherapy to improve tumor microenvironment of pancreatic cancer

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