Down-regulation of HLA class I antigen-processing machinery components in esophageal squamous cell carcinomas: Association with disease progression

Liu, Qiao; Hao, Chunyan; Su, Peng; Shi, Jingxue

doi:10.1080/00365520902998679

Cited by 36 publications

(34 citation statements)

References 29 publications

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“…Relapse-free survival increased significantly in the MHC class I-positive patients compared to the negative patients in the total patient group and the chemotherapy-only group, but not in the PSK group. PSK, protein-bound polysaccharide K. prognosis have been reported to be correlated in various types of cancer, including breast, lung, renal cell carcinoma and colon cancer (8,9,(17)(18)(19). The present study found that the expression rate of MHC class I in primary gastric cancer lesions was 55%, close to the values that have been reported in other studies (20).…”

Section: Correlation Between Expression Of Mhc Class I and Efficacy Osupporting

confidence: 79%

“…In esophageal cancer, MHC class I expression in metastatic lymph nodes was found to be depressed compared to that in the primary lesion (9). That is, cancer cells that have evaded the host immune response are considered to be able to readily form metastatic foci in the lymph nodes.…”

Section: Correlation Between Expression Of Mhc Class I and Efficacy Omentioning

confidence: 99%

“…In particular, decreased expression of MHC class I by the tumor is one mechanism which allows evasion of cytotoxic T lymphocytes (CTLs), which play a central role in tumor immunity (6). This has been reported to correlate with a poor prognosis for various types of cancer, including gastric cancer (7)(8)(9).…”

Section: Introductionmentioning

confidence: 99%

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Correlation between efficacy of PSK postoperative adjuvant immunochemotherapy for gastric cancer and expression of MHC class I

Ito

Tanaka

Ohira

et al. 2012

Experimental and Therapeutic Medicine

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Abstract. Protein-bound polysaccharide K (PSK) is a glycoprotein that is purified from the mushroom Coriolus versicolor. In Japan, PSK is clinically used in combination with anticancer agents following gastric cancer surgery. Evaluation of the response is difficult, as efficacy is determined via antitumor immunoenhancing effects, and for that reason PSK has not become a standard therapy. The present study evaluated the expression of MHC class I in gastric cancer patients who received PSK postoperative adjuvant immunochemotherapy, and investigated the correlation between MHC class I expression and clinical outcomes. The subjects comprised 349 patients with stage II/III gastric cancer, who had received adjuvant therapy following curative resection between 1995 and 2008. MHC class I expression in the primary lesion was evaluated by immunohistochemical staining. Patients were divided into two treatment groups: one was only administered oral chemotherapy (chemotherapy-only group) and the other was administered chemotherapy plus PSK (PSK group). The clinical outcomes were compared between the two groups. The two groups did not differ in regard to their MHC class I expression. Expression-negative cases demonstrated 3-year recurrence-free survival (RFS) rates of 65% in the PSK group and 47% in the chemotherapy-only group. Therefore, the PSK group revealed a prolonged survival. For the 82 expressionnegative cases with pN2 or greater, the RFS rates were 68% in the PSK group and 28% in the chemotherapy-only group, representing a significant difference. Thus, PSK adjuvant immunochemotherapy may be effective in MHC class I-negative patients, who are in a state of antitumor immunological tolerance, and patients with advanced lymph node metastasis of pN2 or greater. IntroductionIn Japan, adjuvant therapy using S-1 is considered effective for stage II/III gastric cancer. However, postoperative recurrence is observed in 30% of stage III patients, and the efficacy of S-1 monotherapy is marginal (1). Thus, combination of S-1 with various anticancer agents is being tested. Protein-bound polysaccharide K (PSK) is a glycoprotein extracted from the mushroom Coriolus versicolor belonging to the Polyporaceae family (2). Use of this antitumor agent is approved by the Japanese health insurance system, and has been confirmed to prolong survival in gastric cancer patients. PSK is considered to demonstrate not only direct cytocidal activity, but also antitumor immunoenhancing effects (3,4). However, the mechanisms of these effects remain unclear, and in addition, since 1994 no studies have reported any clinical efficacy of PSK against gastric cancer, thus this agent has not been recognized as a standard therapy (5).The fact that hosts become immunocompromised at the time of tumor progression has long been considered to be significant. In particular, decreased expression of MHC class I by the tumor is one mechanism which allows evasion of cytotoxic T lymphocytes (CTLs), which play a central role in tumor immunity (6). This has been reported t...

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Section: Correlation Between Expression Of Mhc Class I and Efficacy Osupporting

confidence: 79%

Section: Correlation Between Expression Of Mhc Class I and Efficacy Omentioning

confidence: 99%

See 1 more Smart Citation

Correlation between efficacy of PSK postoperative adjuvant immunochemotherapy for gastric cancer and expression of MHC class I

Ito

Tanaka

Ohira

et al. 2012

Experimental and Therapeutic Medicine

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“…33 Previous study indicated that downregulation of HLA class I molecules in the tumor was associated with a poor prognosis in esophageal squamous cell carcinoma (ESCC) patients and defects of HLA class I antigen-processing machinery components, including b 2 -microglobulin (b 2 m), transporters associated with antigen presentation (TAP)1, large multifunctional proteasome (LMP) 2 and LMP7, in ESCC patients was related to disease progression. 34,35 However, little information was available for the clinical relevance of HLA-G, both the primary tumor HLA-G expression and sHLA-G in plasma in particular, in ESCC. An early study indicated that HLA-G expression was associated with a poor survival in ESCC patients.…”

mentioning

confidence: 99%

Human leukocyte antigen‐G expression is associated with a poor prognosis in patients with esophageal squamous cell carcinoma

Lin

Zhang

Zhou

et al. 2011

Intl Journal of Cancer

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Human leukocyte antigen (HLA)‐G inhibits functions of immune component cells and promotes malignant cells evading from antitumor immunity. We investigated the clinical relevance of HLA‐G expression in esophageal squamous cell carcinoma (ESCC). In our study, HLA‐G expression in 79 primary ESCC lesions and corresponding adjacent normal tissues were analyzed with immunohistochemistry. Soluble HLA‐G (sHLA‐G) in plasma was detected with enzyme‐linked immunosorbent assay (ELISA) in 41 ESCC patients (including 19 case‐matched lesions and plasma samples) and in 153 normal healthy controls. HLA‐G expression was observed in 65.8% (52/79) of the ESCC lesions but not in adjacent normal esophageal tissues. HLA‐G expression was more frequently observed in patients with advanced disease stage (III/IV vs. I/II, p = 0.01). Patients with HLA‐G expression had a significantly worse survival, and HLA‐G could be an independent prognostic factor. sHLA‐G levels in plasma were significantly increased in patients compared to normal controls (median: 152.4 U/ml vs. 8.9 U/ml, p < 0.001). The area under receiver‐operating characteristic (ROC) curve for sHLA‐G in plasma was 0.992. However, no significant correlation was found between sHLA‐G in plasma and clinical parameters studied. In conclusion, our findings indicated that HLA‐G expression in ESCC is associated with poor survival and could be a prognostic indicator. Furthermore, increased levels of sHLA‐G in plasma might be a useful preoperative biomarker for diagnosis.

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“…An association between the downregulation of TAP-1, TAP-2 and HLA-I expression and cancer prognosis has been reported in a wide range of malignancies (21)(22)(23)(24). The correlation between TAP-1, TAP-2 and HLA-I and prognosis in NPC has been investigated (25).…”

Section: Discussionmentioning

confidence: 99%

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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Down-regulation of HLA class I antigen-processing machinery components in esophageal squamous cell carcinomas: Association with disease progression

Abstract: Our results indicate that lack or reduction of HLA class I antigens and expression of APM components in ESCC may render some tumor cells to escape the immunosurveillance mediated by CD8(+) T cells and contribute to the clinical course of ESCC.

Cited by 36 publications

References 29 publications

Correlation between efficacy of PSK postoperative adjuvant immunochemotherapy for gastric cancer and expression of MHC class I

Correlation between efficacy of PSK postoperative adjuvant immunochemotherapy for gastric cancer and expression of MHC class I

Human leukocyte antigen‐G expression is associated with a poor prognosis in patients with esophageal squamous cell carcinoma

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

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