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Brachyury is a transcription factor belonging to the T-box gene family and is involved in the posterior formation of the mesoderm and differentiation of chordates. As the overexpression of Brachyury is a poor prognostic factor in a variety of cancers, the establishment of Brachyury-targeted therapy would be bene cial for the treatment of aggressive tumors. Because transcription factors are di cult to treat with a therapeutic antibody, peptide vaccines are a feasible approach for targeting Brachyury. In this study, we identi ed Brachyury-derived epitopes that elicit antigen-speci c and tumor-reactive CD4 + T cells that directly kill tumors. T cells recognizing Brachyury epitopes were present in patients with head and neck squamous cell carcinoma. Next, we focused on gemcitabine (GEM) as an immunoadjuvant to augment the e cacy of antitumor responses by T cells. Interestingly, GEM upregulated HLA class I and HLA-DR expression in tumor, followed by the upregulation of anti-tumor T-cell responses. As tumoral PD-L1 expression was also augmented by GEM, PD-1/PD-L1 blockade and GEM synergistically enhanced the tumor-reactivity of Brachyury-reactive T cells. The synergy between the PD-1/PD-L1 blockade and GEM was also con rmed in a mouse model of head and neck squamous cell carcinoma. These results suggest that the combined treatment of Brachyury peptide with GEM and immune checkpoint blockade could be a promising immunotherapy against head and neck cancer.

We previously reported on a hands-on seminar on basic research organized at the rd Annual Meeting of the Japanese Rhinologic Society Osaka, Japan in order to not only improve individual skills and knowledge but also enhance interaction and collaboration between researchers. A questionnaire survey was also conducted following this seminar. Moreover, we investigated the shift in the number of basic oral and poster presentations at the annual meetings of the Japanese Rhinologic Society from to. In this previous report, % of participants agreed that the seminar was useful and most hoped to continue such seminars in the future. The percentage of basic oral and poster presentations at the meeting decreased to % compared with % at the meeting. Thus, to further develop this seminar on basic research, we again organized at the th Annual Meeting of the Japanese Rhinologic Society Hiroshima, Japan a second hands-on seminar on basic research for clinicians, focusing on how to prepare good frozen sections, obtain good DNA and RNA, and perform reverse transcription polymerase chain reaction RT-PCR. Here, we present an outline of this second seminar and discuss detailed procedures for performing Kawamoto's film method, which is a new technique with adhesive film for the preparation of multipurpose fresh-frozen sections from hard tissues, and for collecting DNA and RNA from nasal tissue. Additionally, we present the results of a questionnaire survey and the percentage of basic oral and poster presentations in this seminar as last year, as well as discuss perspective of this trial.

Brachyury is a transcription factor belonging to the T-box gene family and is involved in the posterior formation of the mesoderm and differentiation of chordates. As the overexpression of Brachyury is a poor prognostic factor in a variety of cancers, the establishment of Brachyury-targeted therapy would be beneficial for the treatment of aggressive tumors. Because transcription factors are difficult to treat with a therapeutic antibody, peptide vaccines are a feasible approach for targeting Brachyury. In this study, we identified Brachyury-derived epitopes that elicit antigen-specific and tumor-reactive CD4+ T cells that directly kill tumors. T cells recognizing Brachyury epitopes were present in patients with head and neck squamous cell carcinoma. Next, we focused on gemcitabine (GEM) as an immunoadjuvant to augment the efficacy of antitumor responses by T cells. Interestingly, GEM upregulated HLA class I and HLA-DR expression in tumor, followed by the upregulation of anti-tumor T-cell responses. As tumoral PD-L1 expression was also augmented by GEM, PD-1/PD-L1 blockade and GEM synergistically enhanced the tumor-reactivity of Brachyury-reactive T cells. The synergy between the PD-1/PD-L1 blockade and GEM was also confirmed in a mouse model of head and neck squamous cell carcinoma. These results suggest that the combined treatment of Brachyury peptide with GEM and immune checkpoint blockade could be a promising immunotherapy against head and neck cancer.

No abstract