森本 侑樹

Carcinoma ex pleomorphic adenoma (CXPA) is a rare malignant salivary gland tumor, and its prognosis is determined by the histological progression beyond the adenoma capsule. However, a preoperative evaluation of the histological progression remains challenging, and there is no consensus regarding treatment strategies for CXPA. Herein, we aimed to predict the histological progression preoperatively and develop an appropriate treatment strategy for CXPA. We retrospectively reviewed 22 patients with parotid gland CXPA recorded at our hospital. The clinicopathological characteristics were assessed, and survival analysis was performed. T3≤ or N+ were common in widely invasive CXPA (WICXPA) (p < 0.05). A tumor diameter > 40 mm and the N+ status were associated with poor prognosis considering overall survival (OS) and locoregional recurrence rate (LRC) (p < 0.05). Patients with facial nerve paralysis exhibited better OS and LRC than those without facial nerve paralysis. More than 90% of patients with WICXPA experienced distant metastases. Meanwhile, there were no cases of recurrence or death due to intracapsular and minimally invasive CXPA. A preoperative advanced T stage or N+ status was suspected as WICXPA. Tumors > 40 mm in size and N+ status necessitate high-intensity local treatment. Facial nerve invasion can be controlled by nerve resection. Postoperative systemic therapy could control distant metastases.

Allergic conjunctivitis is a chronic inflammatory disease that is characterized by severe itch in the conjunctiva, but how neuro-immune interactions shape the pathogenesis of severe itch remains unclear. We identified a subset of memory-type pathogenic Th2 cells that preferentially expressed Il1rl1-encoding ST2 and Calca-encoding calcitonin-gene-related peptide (CGRP) in the inflammatory conjunctiva using a single-cell analysis. The IL-33-ST2 axis in memory Th2 cells controlled the axonal elongation of the peripheral sensory C-fiber and the induction of severe itch. Pharmacological blockade and genetic deletion of CGRP signaling in vivo attenuated scratching behavior. The analysis of giant papillae from patients with severe allergic conjunctivitis revealed ectopic lymphoid structure formation with the accumulation of IL-33-producing epithelial cells and CGRP-producing pathogenic CD4+ T cells accompanied by peripheral nerve elongation. Thus, the IL-33-ST2-CGRP axis directs severe itch with neuro-reconstruction in the inflammatory conjunctiva and is a potential therapeutic target for severe itch in allergic conjunctivitis.

アレルギー疾患はいまだ根治的治療法がなく、病態形成機構をはじめさまざまな側面で精力的に研究がなされており、アレルギー性炎症を誘導する2型自然リンパ球の同定、病原性Th2細胞の同定、粘膜上皮細胞由来の上皮性サイトカインとしてのIL-33、IL-25、TSLPの作用機序などが近年明らかになってきている。本稿では、アレルギー性気道炎症の病態制御について以下の項目で概説した。1)自然免疫と獲得免疫、2)病原性Th2細胞-Pathogenic Th2 cells-の同定とIL-33による誘導、3)線維化誘導-病原性ヘルパーT細胞、4)CD69-Myl9システムによる活性化T細胞の気道炎症巣へのリクルート。