Identification of human leukocyte antigen‐A24‐restricted epitope peptides derived from gene products upregulated in lung and esophageal cancers as novel targets for immunotherapy

Suda, Takako; Tsunoda, Takuya; Daigo, Yataro; Nakamura, Yusuke; Tahara, Hideaki

doi:10.1111/j.1349-7006.2007.00603.x

Cited by 110 publications

(105 citation statements)

References 42 publications

(44 reference statements)

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“…Cytotoxic T cell lines and clones against LY6K peptide were generated by repeated stimulation with mature DCs pulsed with LY6K peptide (22). As shown in Supplemental Fig.…”

Section: Inhibition Of Mapk Signaling Results In Enhancement Of Tumormentioning

confidence: 99%

The MAPK Pathway Is a Predominant Regulator of HLA-A Expression in Esophageal and Gastric Cancer

Mimura

Shiraishi

Müeller

et al. 2013

The Journal of Immunology

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Downregulation of HLA class I expression may contribute to a poor prognosis in cancer patients. There is limited information about epigenetic and oncogenic regulation of HLA class I, and multiple mechanisms may be involved. In the current study, we examined the relationship between the HER2-signaling pathway (MAPK and PI3K-Akt) and the expression of HLA class I and Ag-processing machinery (APM) components. A panel of gastric and esophageal cancer cell lines was treated with wortmannin as an Akt-signal inhibitor; the MAPK signal inhibitor PD98059; lapatinib, which inhibits both the epidermal growth factor receptor and HER2 tyrosine kinase; or siRNA for MAPK. The levels of HER2-signaling molecules, APM components, and HLA class I were evaluated by Western blot, quantitative PCR, and flow cytometry. Resected gastric tumor tissues (n = 102) were analyzed for p-Erk and HLA class I expression by immunohistochemistry. As a result, inhibition of the MAPK pathway induced upregulation of HLA-A02 and HLA-A24 expression in parallel with an increase in APM components and enhanced target sensitivity to tumor Ag–specific CTL lysis. HLA-A expression was predominantly regulated by the MAPK pathway, but it was also influenced, in part, by the Akt pathway. There was a strong inverse correlation between p-Erk expression and HLA class I expression in clinical tumor samples. In conclusion, HLA-A expression is predominantly regulated by the MAPK pathway in gastric and esophageal cancer.

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“…Cytotoxic T cell lines and clones against LY6K peptide were generated by repeated stimulation with mature DCs pulsed with LY6K peptide (22). As shown in Supplemental Fig.…”

Section: Inhibition Of Mapk Signaling Results In Enhancement Of Tumormentioning

confidence: 99%

The MAPK Pathway Is a Predominant Regulator of HLA-A Expression in Esophageal and Gastric Cancer

Mimura

Shiraishi

Müeller

et al. 2013

The Journal of Immunology

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“…We have recently identified several novel HLA class I-restricted epitopes presented on ESCC and recognized by tumor-specific T cells through the genome-wide approach (18)(19)(20). Our gene expression profile data indicated that cancer-testis antigens such as TTK protein kinase (TTK), lymphocyte antigen 6 complex locus K (LY6K), cell division cycle associated 1 (CDCA1), 34 kDa translocase of the outer mitochondrial membrane (TOMM34), hypoxia-inducible protein 2 (HIG2), and insulin-like growth factor (IGF)-II mRNAbinding protein 3 (IMP3) were highly expressed in ESCC (18)(19)(20)(21)(22)(23)(24)(25). Peptides derived from these cancer-testis antigens could stimulate CTL that recognize and kill ESCC cells endogenously expressing these antigens (18,19,23).…”

Section: Introductionmentioning

confidence: 98%

“…Our gene expression profile data indicated that cancer-testis antigens such as TTK protein kinase (TTK), lymphocyte antigen 6 complex locus K (LY6K), cell division cycle associated 1 (CDCA1), 34 kDa translocase of the outer mitochondrial membrane (TOMM34), hypoxia-inducible protein 2 (HIG2), and insulin-like growth factor (IGF)-II mRNAbinding protein 3 (IMP3) were highly expressed in ESCC (18)(19)(20)(21)(22)(23)(24)(25). Peptides derived from these cancer-testis antigens could stimulate CTL that recognize and kill ESCC cells endogenously expressing these antigens (18,19,23). Furthermore, we have established a reliable in vitro assay system using peripheral blood lymphocytes (PBL) to detect tumor-specific CTL responses against the panels of HLA class I epitopes derived from these cancer-testis antigens (18,19).…”

Section: Introductionmentioning

confidence: 99%

Immunogenic Tumor Cell Death Induced by Chemoradiotherapy in Patients with Esophageal Squamous Cell Carcinoma

et al. 2012

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Although it has been shown that chemoradiotherapy may induce immunogenic cell death, which could trigger T-cell immunity mediated by high-mobility group box 1 protein (HMGB1) and calreticulin, there is still limited information to support this theory directly in a clinical setting. In the present study, we evaluated antigen-specific T-cell responses against six cancer-testis antigens in peripheral blood lymphocytes from patients with esophageal squamous cell carcinoma (ESCC) receiving chemoradiation. Expression of HMGB1 and calreticulin within tumor microenvironment was also analyzed in resected samples with and without chemoradiotherapy in relation to patients survival. Tumor antigen-specific T-cell responses were confirmed in six (38%) of 16 patients with ESCC after chemoradiotherapy coexisting with elevated serum HMGB1. In addition, HMGB1 within tumor microenvironment was significantly upregulated in patients with ESCC with preoperative chemoradiotherapy, but not in those without chemoradiotherapy, and the degree of HMGB1 positively correlated with patient survival (n ¼ 88). Both irradiation and chemotherapeutic drugs induced upregulation of HMGB1 and calreticulin in nine ESCC cell lines. Furthermore, HMGB1 was able to induce maturation of dendritic cells. Together, our findings indicate that chemoradiation induces tumor antigen-specific T-cell responses, and HMGB1 production is related to clinical outcome after chemoradiation. Cancer Res; 72(16); 3967-76. Ó2012 AACR.

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“…The targeting oncogenic antigens can avoid the immune escape of cancer cells by lacking these proteins [22,23] . Epitope peptides of several oncoantigens such as kinesin family member 20A (KIF20A), lymphocyte antigen 6 complex locus K (LY6K), DEP domain-containing 1 (DEPDC1), forkhead box M1 (FOXM1), cell division cycleassociated 1 (CDCA1), cadherin 3/P-cadherin (CDH3), insulin-like growth factor-II mRNAbinding protein 3 (IMP-3) and others have been developed for clinical trials [24][25][26][27][28][29][30][31][32][33] .…”

Section: Oncoantigensmentioning

confidence: 99%

Cancer vaccine therapy based on peptides

Katsuda

Yamaue

2017

Trends Immunother

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Following numerous unequivocal clinical failures, immunotherapy has become an attractive therapeutic modality. Peptide vaccines are cost-effective compared to other vaccine approaches, and effective epitopes eliciting strong immune response can be selected experimentally in silico and ex vivo. However, the clinical benefits of cancer peptides vaccine have been disappointing in most studies; therefore, we need to prove the clinical beneficial effects for cancer treatment following induction of more powerful cytotoxic T lymphocytes (CTLs). First, the choice of ideal target antigen is essential. Epitopes derived from tumor-associated antigens (TAAs), oncoantigens, vascular endothelial cells and neoantigens are then developed. In particular, wholeexome sequencing enables us to identify the epitopes of neoantigens. The choice of therapeutic objectives is also important and peptide vaccines might be better to be developed as preventative vaccines. Dendritic cells (DCs) vaccine pulsed with peptides is an approach to induce powerful CTLs and might overcome several disadvantages of peptide vaccines as monotherapy. Targeting vaccine therapy against DC subsets in vivo is under development.

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Identification of human leukocyte antigen‐A24‐restricted epitope peptides derived from gene products upregulated in lung and esophageal cancers as novel targets for immunotherapy

Cited by 110 publications

References 42 publications

The MAPK Pathway Is a Predominant Regulator of HLA-A Expression in Esophageal and Gastric Cancer

The MAPK Pathway Is a Predominant Regulator of HLA-A Expression in Esophageal and Gastric Cancer

Immunogenic Tumor Cell Death Induced by Chemoradiotherapy in Patients with Esophageal Squamous Cell Carcinoma

Cancer vaccine therapy based on peptides

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