HLA-A2 Antigen status predicts metastasis and response to immunotherapy in gastric cancer

Ogoshi, Kyoji; Tajima, Tomoo; Mitomi, T; Makuuchi, Hiroyasu; Tsuji, Kimiyoshi

doi:10.1007/s002620050400

Cited by 17 publications

(14 citation statements)

References 18 publications

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“…Furthermore, we reported that the serum levels of HER-2/neu were correlated with the status of HER-2/neu expression in carcinoma tissue and the serum levels of HER-2/neu may be used to predict the status of HER-2/neu expression. 28 Interestingly, Ogoshi et al 29 reported that HLA-A2-positive patients with gastric cancer had a low risk of lymph-node metastasis and a better response to postoperative immunotherapy with a non-specific immunomodulator, PSK, compared to HLA-A2-negative patients. Furthermore, HLA-A2 alleles were found to be associated with clinical remission by immunotherapy in patients with melanoma.…”

Section: Relationship Between Clinicopathological Features and Hla Hamentioning

confidence: 99%

Frequencies of HER‐2/neu overexpression relating to HLA haplotype in patients with gastric cancer

Kono

Takahashi

Amemiya

et al. 2001

Intl Journal of Cancer

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We have identified that HER-2/neu-derived peptides are naturally processed as tumor rejection antigens recognized by tumor-specific, HLA-A2-restricted cytotoxic T lymphocytes in gastric cancer. To evaluate candidates for immunotherapy using HER-2/neu-derived, HLA-A2-restricted peptides, we examined the frequency of HLA-A2 relating to HER-2/neu overexpression or the infiltrating grade of tumorinfiltrating lymphocytes (TILs) in Japanese patients with gastric cancer. HER-2/neu-overexpressing tumors detected by immunohistochemistry amounted to 19% of primary gastric cancers and HLA-A2-positive patients with gastric cancer were 31% of primary gastric-cancer cases. Finally, gastriccancer patients with both HLA-A2-positive and HER-2/neuoverexpressing tumors amounted to 6.6% of these cases. There was no significant difference in the infiltrating grade of TILs between gastric cancers overexpressing HER-2/neu and those that did not. Gastric cancer is 1 of the most common cancers occurring in Japan today. The control of gastric cancer at advanced stages still remains difficult, despite various treatments such as gastrectomy with extensive lymphadenectomy 1 and surgery combined with chemotherapy. 2 We and others reported that MHC class I-restricted cytotoxic-T lymphocytes (CTLs) from gastric-cancer patients can react specifically against autologous tumor cells. [3][4][5][6] Adoptive immunotherapy based on gastric cancer-specific CTLs, or vaccinations based on the MHC class I-associated tumor antigens that they recognize, represent alternative therapeutic approaches. The presence of tumor-associated antigens recognized by gastric-cancer-specific CTLs restricted by HLA-A31 6 or HLA-A2.1 molecules 4 has been demonstrated, although the nature of these antigens has not been defined. Moreover, we have identified that HER-2/neu-derived peptides are naturally processed as tumorassociated antigens recognized by tumor-specific, HLA-A2-restricted CTLs in gastric cancer. 7 Thus, HER-2/neu-derived peptides may be considered as candidates for tumor-specific immunotherapy such as tumor vaccination in patients with gastric cancer.The HER-2/neu protooncogene encodes a 185-kDa transmembrane glycoprotein with tyrosine-specific kinase activity. 8 The HER-2/neu protooncogene is amplified and overexpressed in approximately 30% of human ovarian and breast tumors 9 and in 20% of gastric cancers. 10 HLA-A2-restricted CTL epitopes derived from HER2/neu recognized by ovarian-11,12 and breast-13 cancerspecific CTLs have previously been defined, in addition to those specific for gastric cancer. The identification of several new HLA-A2-restricted CTL epitopes from HER-2/neu that can activate CTLs from healthy donors and patients with advanced ovarian carcinoma has also been reported. 14,15 These results indicate that HER-2/neu-derived peptides could be broad targets for immunotherapy against these types of cancers. It is important to evaluate candidates for tumor vaccination with HER-2/neu-derived peptides in patients with gastric cancer. Because it has...

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Section: Relationship Between Clinicopathological Features and Hla Hamentioning

confidence: 99%

Frequencies of HER‐2/neu overexpression relating to HLA haplotype in patients with gastric cancer

Kono

Takahashi

Amemiya

et al. 2001

Intl Journal of Cancer

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“…Here, we has further confirmed the involvement of HLA-A2 in breast cancer as significant higher expression of HLA-A2/A30 and HLA-A2/A31 haplotype as well as HLA-A30 and A31 alleles in breast cancer patients were reported (Table 3). HLA-A2 has been associated with poor disease outcome in breast [18,21], lung [22], ovarian [23], colorectal [24] and gastric cancer [8,25]. HLA-A2 ?…”

Section: Discussionmentioning

confidence: 99%

“…Both HLA class I (-A, -B and -C) and class II (-DR, -DP and -DQ) molecules have been associated with more than 100 diseases including autoimmunity [2] and malignancy [3][4][5][6]. The HLA molecules have been used as a guide for treatment options [7,8] and as prognostic factors in several diseases [9]. However, the underlying molecular mechanisms that involve HLA molecules in disease progression are still poorly understood [10].…”

Section: Introductionmentioning

confidence: 99%

HLA-A and breast cancer in West Peninsular Malaysia

et al. 2010

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Breast cancer is the most common malignancy among females in Malaysia. Attempts have been made to investigate the association between breast cancer and human leukocyte antigen (HLA) types. However, data from those previous studies are highly variable. The aim of this study is to investigate the association between HLA-A types and clinicopathological factors in breast cancer. The frequencies of HLA-A type in 59 female patients with infiltrating ductal of the breast were determined by polymerase chain reaction method. HLA-A2/A30 and A2/A31 haplotype (5.1%; P = 0.045) as well as HLA-A30 (5.1%, P = 0.045) and A31 (6.8%; P = 0.020) allele were significant higher in the patients than controls (0%). HLA-A24 allele was negatively related to lymph node metastasis (r = -0.316; P = 0.021) whereas, A26 (r = -0.430; P = 0.001) and A36 (r = -0.430; P = 0.001) alleles were negatively correlated to distant metastasis in breast cancer. Negative correlations between HLA-A26/A36 (r = -0.430; P = 0.001), A2/A11 (r = -0.276; P = 0.044), A24/A34 (r = -0.430; P = 0.001) haplotypes and distant metastasis were identified. Interestingly, Her2 expression in breast carcinoma was negatively correlated to A11/24 haplotypes (r = -0.294; P = 0.034) but positively correlated to homozygous HLA-A24 (r = 0.396; P = 0.040). In conclusion, HLA-A2, -A30 and A31 were associated with breast cancer.

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“…The mechanisms of action of PSK has been extensively investigated by molecular biological techniques (Fujii, 1996) and are known to include the following: 1) direct toxicity for cancer cells, 2) induction of immune cells and cytokines involved in host defenses, and 3) inhibition of immunosuppressants that are produced in the tumor-bearing state. Several authors have reported on parameters for selecting good responders to PSK, and these include gastric cancer patients with a serum immunosuppressive acidic protein level of less than 580 ratio of 2.0 or more, and carriers of HLA-A2 antigen (Ogoshi, Tajima, et al, 1997;Toge and Yamaguchi, 2000). Another study showed that PSK could decrease IL-6-and IL-10-producing cells, thereby altering the Th1/Th2 balance of CD4+ helper cells and leading to Th1 predominance (Shibata, Nezu, et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

Efficacy of Postoperative Adjuvant Oral Immunochemotherapy in Patients With Dukes' B Colorectal Cancer

Mukai

Tajima

Nakasaki

et al. 2003

ACRT

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Among 370 patients who underwent radical resection of primary colorectal cancer over a 17-year period, 167 had stage II-Dukes' B cancer. After excluding 10 patients treated with intravenous drugs other than 5-FU or hepatic arterial injection and 11 patients with rare histological types other than typical differentiated adenocarcinoma, the remaining 146 patients were used to assess the utility of Japanese-style oral postoperative adjuvant immunochemotherapy. Ninety-one patients who received oral chemotherapy with/without immunotherapy as postoperative adjuvant therapy had a 5-year survival rate of 89.1%, while the rate was 66.5% for patients without such therapy (non-chemotherapy; n=55, p=0.0015). When the 91 patients were divided into those treated with chemotherapy plus immunotherapy (immunochemotherapy; n=61) and those treated with chemotherapy alone (chemotherapy-only; n=30), the 5-year survival rates of the immunochemotherapy, chemotherapy-only, and non-chemotherapy groups were 92.2%, 83.5%, and 66.5%, respectively (immunochemotherapy vs. non-chemotherapy, p=0.0022). When 30 patients were selected from each of the 3 groups and compared by the propensity score matching method, a significant difference was found between the immunochemotherapy and chemotherapy-only groups (p=0.0364), as well as between the immunochemotherapy and non-chemotherapy groups (p=0.0055). These results suggest that Japanese-style oral immunochemotherapy is useful as postoperative adjuvant therapy in patients with stage II-Dukes' B colorectal cancer.

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HLA-A2 Antigen status predicts metastasis and response to immunotherapy in gastric cancer

Cited by 17 publications

References 18 publications

Frequencies of HER‐2/neu overexpression relating to HLA haplotype in patients with gastric cancer

Frequencies of HER‐2/neu overexpression relating to HLA haplotype in patients with gastric cancer

HLA-A and breast cancer in West Peninsular Malaysia

Efficacy of Postoperative Adjuvant Oral Immunochemotherapy in Patients With Dukes' B Colorectal Cancer

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