Basophil-Derived IL-4 Production and Its Potential Pro-Tumoural Role in Th2-Polarisation Within Sentinel Lymph Nodes of Primary Cutaneous Melanoma

IF 3.5 3区医学 Q1 DERMATOLOGY

Experimental Dermatology Pub Date : 2025-01-25 DOI:10.1111/exd.70028

Aki Tajima, Fumikazu Yamazaki, Izumi Kishimoto, Ni Ma, Noriko Kume, Andrew F. Walls, Naotomo Kambe, Hideaki Tanizaki

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Abstract

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.

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嗜碱性粒细胞来源的IL-4的产生及其在原发性皮肤黑色素瘤前哨淋巴结内th2极化中的潜在促瘤作用

肿瘤微环境（TME）中的慢性炎症通过th2极化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，它的来源仍然未知。嗜碱性粒细胞被认为是其来源之一。嗜碱性粒细胞衍生的IL-4有助于寄生虫感染和过敏性疾病的th2极化，并与肿瘤免疫有关。鉴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，并证明嗜碱性粒细胞产生IL-4。免疫组织化学（IHC）与嗜碱性粒细胞特异性BB1抗体和原位杂交。在II期或更晚，嗜碱性粒细胞倾向于浸润皮肤病变。浸润的嗜碱性细胞数量越多，与Breslow深度和较短的无进展生存期相关，表明与不良预后相关。在sln中，嗜碱性细胞在早期浸润而无转移（I期和II期），浸润的嗜碱性细胞数量在II期明显高于I期。IHC显示，与I期sln相比，IL-4水平在II期sln中也显著升高。此外，浸润sln的嗜碱性细胞数量与IL-4表达呈正相关。原位杂交证实嗜碱性细胞表达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，并表明嗜碱性细胞衍生的IL-4可能通过th2极化促进sln的转移。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。

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来源期刊

Experimental Dermatology 医学-皮肤病学

CiteScore

6.70

自引率

5.60%

发文量

201

审稿时长

2 months

期刊介绍： Experimental Dermatology provides a vehicle for the rapid publication of innovative and definitive reports, letters to the editor and review articles covering all aspects of experimental dermatology. Preference is given to papers of immediate importance to other investigators, either by virtue of their new methodology, experimental data or new ideas. The essential criteria for publication are clarity, experimental soundness and novelty. Letters to the editor related to published reports may also be accepted, provided that they are short and scientifically relevant to the reports mentioned, in order to provide a continuing forum for discussion. Review articles represent a state-of-the-art overview and are invited by the editors.