Figure S1, S2, S3, S4, S5, S6, S7, S8, S9, S10, S11

Acute arterial hemorrhage is a damaging and sometimes lethal complication that occurs in patients with head and neck cancer. However, achieving hemostasis can be challenging because of the difficulty in applying pressure in the throat and oral cavity. In this context, endovascular treatment (ET) has been performed in recent years. This report aims to describe the benefits of ET for acute bleeding. Additionally, our findings emphasize the importance of early diagnosis and treatment of tumor-related bleeding, not only for immediate life-saving benefits but also for the potential resumption of irradiation and chemotherapy, which can lead to favorable long-term prognoses in some instances. We describe two cases of primary tumor bleeding where treatment was successful with ET. Neurosurgeons performed these treatments, and effective hemostasis was achieved in both cases. No complications or rebleeding were observed. ET is a better option for hemorrhage from oropharyngeal tumors than for hemorrhage from the main trunk of the carotid artery. The efficacy of ET is dependent on the vessels involved, and early identification of the culprit artery can predict the prognosis. ET should be considered an option for acute arterial hemorrhage in head and neck cancer.

It is difficult to anatomically understand the three-dimensional structure of the middle ear and temporal bone during surgery, and great surgical technique are required. Therefore, complications are avoided through simulation using a three-dimensional printer, which was effective in not only safe and reliable surgery but also educating young physicians.

Preoperative simulation using a three‐dimensional printer is effective to perform safe surgery by knowing the range limit of drilling in the temporal bone. Moreover, simulations using models are thought to be useful for education of young surgeon.

AbstractTumor-specific CD8+ T cells play a pivotal role in antitumor immunity and are a key target of immunotherapeutic approaches. Intratumoral CD8+ T cells are heterogeneous; Tcf1+ stemlike CD8+ T cells give rise to their cytotoxic progeny—Tim-3+ terminally differentiated CD8+ T cells. However, where and how this differentiation process occurs has not been elucidated. We herein show that terminally differentiated CD8+ T cells can be generated within tumor-draining lymph nodes (TDLN) and that CD69 expression on tumor-specific CD8+ T cells controls its differentiation process through regulating the expression of the transcription factor TOX. In TDLNs, CD69 deficiency diminished TOX expression in tumor-specific CD8+ T cells, and consequently promoted generation of functional terminally differentiated CD8+ T cells. Anti-CD69 administration promoted the generation of terminally differentiated CD8+ T cells, and the combined use of anti-CD69 and anti–programmed cell death protein 1 (PD-1) showed an efficient antitumor effect. Thus, CD69 is an attractive target for cancer immunotherapy that synergizes with immune checkpoint blockade.

An essential aspect of endoscopic resection for nasal sinus tumors is to ensure an adequate working space and to confirm that the tumor stem is clearly visible. Opening the nasal septum provides an ample working space, but also has a risk of large postoperative perforation of the nasal septum. We encountered a case of malignant

外耳道に発生する悪性腫瘍は極めて稀な疾患である。われわれは2例の外耳道腺様囊胞癌を経験したので報告する。1例目は81歳男性，他院で右外耳道腫瘤摘出後に腺様囊胞癌断端陽性の診断となり，追加切除目的に当院紹介となった。肺結核の既往があり呼吸機能低下から全身麻酔が不可能と判断し，局所麻酔下で側頭骨部分切除術を施行した。永久病理検査で断端陰性，術後15か月時点で局所再発は認めていない。2例目は69歳男性，左耳痛を主訴に当科紹介となった。左外耳道内に充満する腫瘤を認め，生検にて左外耳道腺様囊胞癌と診断，全身麻酔下で側頭骨外側切除術を施行した。永久病理検査で断端陰性，術後12か月時点で局所再発は認めていない。

Anatomical anomalies of the jugular bulb include a high jugular bulb and deficiency of the cortical bone. Most cases are asymptomatic; however, they may present with tinnitus, hearing loss, dizziness. We encountered a rare case of jugular bulb diverticulum with deficiency of the cortical bone that caused objective tinnitus.

If you suspect pulsatile tinnitus from a medical interview, you should check for jugular bulb diverticulum and cortical bone defects on temporal bone CT, in addition to thorough physical examination and contrast-enhanced imaging.

This report is the first to document TEN caused by nivolumab treatment in head and neck cancer. We believe this article can contribute significantly in understanding the principles of nivolumab treatment in patients with head and neck cancer.

While CD69 may regulate thymocyte egress by inhibiting S1P(1) expression, CD69 expression is not thought to be required for normal thymocyte development. Here we show that CD69 is in fact specifically required for the differentiation of mature NKT2 cells, which do not themselves express CD69. Mechanistically, CD69 expression is required on CD24(+) PLZF(hi) innate precursors for their retention in the thymus and completion of their differentiation into mature NKT2 cells. By contrast, CD69-deficient CD24(+) PLZF(hi) innate precursors express S1P1 and prematurely exit the thymus, while S1P1 inhibitor treatment of CD69-deficient mice retains CD24(+) PLZF(hi) innate precursors in the thymus and restores NKT2 cell differentiation. Thus, CD69 prevents S1P1 expression on CD24(+) PLZF(hi) innate precursor cells from aborting NKT2 differentiation in the thymus. This study reveals the importance of CD69 to prolong the thymic residency time of developing immature precursors for proper differentiation of a T cell subset.

The introduction of immune checkpoint inhibitors in cancer treatment highlights the negative regulation of anti-tumor immunity, such as effector T-cell exhaustion in the tumor microenvironment. However, the mechanisms underlying the induction and prevention of T-cell exhaustion remain largely unknown. We found that CD69, a type II glycoprotein known to regulate inflammation through T-cell migration and retention in tissues, plays an important role in inducing the exhaustion of tumor-infiltrating T cells. Cd69-/- mice showed reduced tumor growth and metastasis in a 4T1-luc2 murine breast cancer model, in which increased numbers of tumor-infiltrating lymphocytes, relatively little T-cell exhaustion, and enhanced IFNγ production were observed. Anti-CD69 monoclonal antibody treatment attenuated the T-cell exhaustion and tumor progression in tumor-bearing mice. These findings highlight a novel role of CD69 in controlling the tumor immune escape mediated by T-cell exhaustion and indicate that CD69 is a novel target for cancer immunotherapy.

Background: Biomarkers that enable objective evaluation of the clinical effects of immunotherapy for allergic rhinitis have yet to be identified. Methods: This study included 40 patients who were enrolled in a large randomized, double-blind, placebo-controlled, multicenter study examining the efficacy of sublingual immunotherapy (SLIT) using Japanese cedar (JC) pollen extract during two consecutive pollen seasons from 2010 to 2012. Based on changes in total nasal symptom medication score, patients in the SLIT and placebo groups were subdivided into two subgroups: good responders and poor responders. The levels of JC pollen-specific IL-10+Foxp3+ cells and specific Th2 cytokine-producing cells were measured and the association with the efficacy of SLIT was analysed. Results: The total nasal symptom medication score was significantly lower in the SLIT group compared with the placebo group. The number of JC pollen-specific Th2 cytokine-producing cells increased during the pollen season in the placebo group and in poor responders in the SLIT group; however, the increases were inhibited in the good responders in the SLIT group. The number of JC pollen-specific IL-10+Foxp3+ cells increased only in these good responders. Conclusions: Changes in levels of allergen-specific Th2 cytokine-producing cells and IL-10+Foxp3+ cells could be objective biomarkers for SLIT.