Tajima Aki, Yamazaki Fumikazu, Kishimoto Izumi, Ma Ni, Kume Noriko, Walls Andrew F, Kambe Naotomo, Tanizaki Hideaki
Department of Dermatology, Kansai Medical University, Hirakata, Osaka, Japan.
Department of Dermatology, Tokai University, Isehara, Kanagawa, Japan.
Exp Dermatol. 2025 Jan;34(1):e70028. doi: 10.1111/exd.70028.
Chronic inflammation in the tumour microenvironment (TME) via Th2-polarisation promotes melanoma progression and metastasis, making it a target for immunotherapy. Interleukin (IL)-4 is considered essential for Th2-polarisation in the TME; however, its source remains unknown. Basophils have been postulated as one of its sources. Basophil-derived IL-4 contributes to Th2-polarisation in parasitic infections and allergic diseases and has been implicated in tumour immunity. To identify basophil infiltration into the TME of human melanoma skin lesions and sentinel lymph nodes (SLNs) and demonstrate that basophils produce IL-4. Immunohistochemistry (IHC) with a basophil-specific BB1 antibody and in situ hybridisation. Basophils tended to infiltrate skin lesions at Stage II or later. Higher numbers of infiltrating basophils correlated with the Breslow depth and a shorter progression-free survival, indicating an association with poor prognosis. In SLNs, basophils infiltrated at early stages without metastasis (Stages I and II), with the number of infiltrating basophils being significantly higher in Stage II than in Stage I. IHC revealed that IL-4 levels were also significantly elevated in Stage II SLNs compared to Stage I SLNs. Furthermore, a positive correlation was observed between the number of basophils infiltrating SLNs and IL-4 expression. In situ hybridisation confirmed that basophils expressed IL4. These findings are consistent with previous reports of early-stage melanoma SLNs having a Th2-environment and suggest that basophil-derived IL-4 may contribute to a metastasis-promoting environment in SLNs through Th2-polarisation. Basophils may represent potential immunotherapeutic targets for pro-tumour changes that occur in SLNs in early-stage melanoma.
肿瘤微环境（TME）中通过Th2极化产生的慢性炎症会促进黑色素瘤的进展和转移，使其成为免疫治疗的靶点。白细胞介素（IL）-4被认为是TME中Th2极化所必需的；然而，其来源尚不清楚。嗜碱性粒细胞被假定为其来源之一。嗜碱性粒细胞衍生的IL-4在寄生虫感染和过敏性疾病中有助于Th2极化，并与肿瘤免疫有关。以确定嗜碱性粒细胞浸润到人类黑色素瘤皮肤病变和前哨淋巴结（SLN）的TME中，并证明嗜碱性粒细胞产生IL-4。使用嗜碱性粒细胞特异性BB1抗体进行免疫组织化学（IHC）和原位杂交。嗜碱性粒细胞倾向于在II期或更晚阶段浸润皮肤病变。浸润的嗜碱性粒细胞数量越多，与Breslow深度和无进展生存期越短相关，表明与预后不良有关。在SLN中，嗜碱性粒细胞在无转移的早期阶段（I期和II期）浸润，II期浸润的嗜碱性粒细胞数量明显高于I期。IHC显示，与I期SLN相比，II期SLN中的IL-4水平也显著升高。此外，观察到浸润SLN的嗜碱性粒细胞数量与IL-4表达之间存在正相关。原位杂交证实嗜碱性粒细胞表达IL4。这些发现与先前关于早期黑色素瘤SLN具有Th2环境的报道一致，并表明嗜碱性粒细胞衍生的IL-4可能通过Th2极化促成SLN中的转移促进环境。嗜碱性粒细胞可能代表早期黑色素瘤SLN中发生的促肿瘤变化的潜在免疫治疗靶点。
