Expression of placenta-specific 1 and its potential for eliciting anti-tumor helper T-cell responses in head and neck squamous cell carcinoma

Hayashi, Ryusuke; Nagato, Toshihiro; Kumai, Takumi; Ohara, Kenichi; Ohara, Mizuho; Ohkuri, Takayuki; Hirata-Nozaki, Yui; Harabuchi, Shohei; Kosaka, Akemi; Nagata, Marino; Yajima, Yuki; Yasuda, Syunsuke; Oikawa, Kensuke; Kono, Michihisa; Kishibe, Kan; Takahara, Miki; Katada, Akihiro; Hayashi, Tatsuya; Celis, Esteban; Harabuchi, Yasuaki; Kobayashi, Hiroya

doi:10.1080/2162402x.2020.1856545

Cited by 16 publications

(12 citation statements)

References 59 publications

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“…Interestingly, we detected TWIST1 140–162 peptide‐specific production of not only IFN‐γ but also TNFα and granzyme B in the samples from BC5, BC6, and BC7, indicating that they showed a Th1 cell phenotype (Figure 4). As we had previously demonstrated that granzyme B‐producing HTLs directly killed tumor cells, 31,32 these TWIST1‐specific HTLs would show antitumor cytotoxicity. These results suggested that the TWIST1 140–162 peptide could effectively activate TWIST1‐specific HTLs to enhance cell‐mediated immunity against tumors expressing TWIST1/2.…”

Section: Resultsmentioning

confidence: 94%

A tumor metastasis‐associated molecule TWIST1 is a favorable target for cancer immunotherapy due to its immunogenicity

et al. 2022

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Although neoantigens are one of the most favorable targets in cancer immunotherapy, it is less versatile and costly to apply neoantigen‐derived cancer vaccines to patients due to individual variation. It is, therefore, important to find highly immunogenic antigens between tumor‐specific or associated antigens that are shared among patients. Considering the cancer immunoediting theory, immunogenic tumor cells cannot survive in the early phase of tumor progression including two processes: elimination and equilibrium. We hypothesized that highly immunogenic molecules are allowed to be expressed in tumor cells after an immune suppressive tumor microenvironment was established, if these molecules contribute to tumor survival. In the current study, we focused on TWIST1 as a candidate for highly immunogenic antigens because it is upregulated in tumor cells under hypoxia and promotes tumor metastasis, which is observed in the late phase of tumor progression. We demonstrated that TWIST1 had an immunogenic peptide sequence TWIST1 140–162 , which effectively activated TWIST1‐specific CD4 + T‐cells. In a short‐term culture system, we detected more TWIST1‐specific responses in breast cancer patients compared with in healthy donors. Vaccination with the TWIST1 peptide also showed efficient expansion of TWIST1‐reactive HTLs in humanized mice. These findings indicate that TWIST1 is a highly immunogenic shared antigen and a favorable target for cancer immunotherapy.

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Section: Resultsmentioning

confidence: 94%

A tumor metastasis‐associated molecule TWIST1 is a favorable target for cancer immunotherapy due to its immunogenicity

et al. 2022

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“…Interestingly, recent studies in melanoma suggested that high expression of HLA-DR in tumor cells is associated with improved response rates and clinical benefit of PD-1/PD-L1 targeted therapy. 19 Quite recently, Hayashi et al 29 hypothesized the use of a therapeutic vaccine to effectively stimulate antigenspecific HTLs against a restricted sub-set of laryngeal HLA-DR+ cancers.…”

Section: Discussionmentioning

confidence: 99%

Immunohistochemical detection of “ex novo” HLA‐DR in tumor cells determines clinical outcome in laryngeal cancer patients

Prampolini

Almadori

Bonvissuto

et al. 2021

HLA

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There are controversial results about the role of "ex novo" HLA-DR expression by tumor cells and its correlation with the oncological outcomes. Unfortunately, little is known about HLA-DR expression in laryngeal cancer tumor cells. The main purpose of this retrospective study is to strengthen the usefulness of studying "ex novo" HLA-DR expression on tumor cells from primary laryngeal squamous cell carcinoma (LSCC) patients and investigate its correlation with clinical outcome. We analyzed HLA-DR expression by immunohistochemical analysis in 56 patients with LSCC. The "ex novo" HLA-DR expression on laryngeal cancer tumor cells, assessing non-neoplastic LSCCadjacent tissue, and the association of HLA-DR expression (HLA-DR+) with clinical outcomes were investigated.HLA-DR+ tumor cells were detected in 18/56 LSCC patients (32.1%). All specimens of non-neoplastic laryngeal carcinoma-adjacent tissue resulted HLA-DR negative (HLA-DR-). A statistically significant association was observed between HLA-DR + and well differentiated tumors (G1) (p<0.001). The Kaplan-Meier method showed how HLA-DR+ is significantly associated with both a better disease specific survival (HLA-DR+=100% vs. HLA-DR-=77.4%; p=0.047) and a better relapse free survival (HLA-DR+=100% vs. HLA-DR-=72.3%; p=0.021).Cox regression univariate analysis for death of disease confirmed a higher HR for HLA-DR absence on the surface of epithelial tumor cell [HR:37.489; 95% CI:0.750-18730.776; p=0.253] and for high-grade (G3) tumors [HR:18.601; 95% CI:3.613-95.764; p<0.0001]. Our results confirm that MHC class II HLA-DR expression is activated in a sub-set of LSCC patients. Evaluation of HLA-DR expression in LSCC could be useful for prognosis and future approaches towards personalized therapy.

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“…Despite current state-of-the-art treatments, the recurrence rate of HNCs remains unacceptably high [ 104 ]. In fact, 65% of HNCs recur [ 105 ], and in these cases, the 5-year survival rate for patients with advanced HNC is only 35% to 45% [ 106 , 107 ]. To eliminate this adverse outcome, the treatment of HNCs has begun to adopt immunotherapy strategies [ 108 ].…”

Section: Immunotherapy Of Hncs Associated With T Cellsmentioning

confidence: 99%

T cell effects and mechanisms in immunotherapy of head and neck tumors

et al. 2023

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Head and neck tumors (HNCs) are a common tumor in otorhinolaryngology head and neck surgery, accounting for 5% of all malignant tumors in the body and are the sixth most common malignant tumor worldwide. In the body, immune cells can recognize, kill, and remove HNCs. T cell-mediated antitumor immune activity is the most important antitumor response in the body. T cells have different effects on tumor cells, among which cytotoxic T cells and helper T cells play a major killing and regulating role. T cells recognize tumor cells, activate themselves, differentiate into effector cells, and activate other mechanisms to induce antitumor effects. In this review, the immune effects and antitumor mechanisms mediated by T cells are systematically described from the perspective of immunology, and the application of new immunotherapy methods related to T cells are discussed, with the objective of providing a theoretical basis for exploring and forming new antitumor treatment strategies.

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Expression of placenta-specific 1 and its potential for eliciting anti-tumor helper T-cell responses in head and neck squamous cell carcinoma

Cited by 16 publications

References 59 publications

A tumor metastasis‐associated molecule TWIST1 is a favorable target for cancer immunotherapy due to its immunogenicity

A tumor metastasis‐associated molecule TWIST1 is a favorable target for cancer immunotherapy due to its immunogenicity

Immunohistochemical detection of “ex novo” HLA‐DR in tumor cells determines clinical outcome in laryngeal cancer patients

T cell effects and mechanisms in immunotherapy of head and neck tumors

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