高内皮微静脉(HEV)为肿瘤浸润淋巴细胞(TILs)进入肿瘤组织的门户，HEV数量与肿瘤患者预后及免疫治疗疗效正相关。文献报道炎症时M1型巨噬细胞(Mɸ)可通过TNF-α-TNFR通路活化血管平滑肌细胞，促进粥样硬化动脉外膜三级淋巴组织(TLS)中HEV生成。然而，黑素瘤中M1样肿瘤相关巨噬细胞(TAM)能否诱导肿瘤局部HEV形成仍未知。我们前期研究表明，缺氧Mɸ中HIF-1α表达上调，可向M1样表型转化并分泌大量TNF-α。将其输入清除Mɸ的荷瘤鼠可促进黑素瘤局部HEV生成。据此我们推测黑素瘤早期缺氧下，TAM内HIF-1α表达上调，向M1样TNF-αhiMHC-IIhiTAM分化，激活肿瘤内血管内皮细胞中TNF-α-TNFR通路，诱导HEV形成，进而增加TILs数量抑制肿瘤进展。基于此，本研究拟通过动物模型结合临床标本验证上述假说，从而为以M1样TAM为靶点的黑素瘤免疫治疗提供新思路。

High endothelial venule (HEV) is the portal of tumor infiltrating lymphocytes (TILs) into tumor tissues. The number of HEV is positively correlated with the prognosis of patients and the efficacy of immunotherapy.It has been reported that M1 Mɸ could activate VSMC in lesional arteries via TNF-α-TNFR pathway to promote HEV formation in TLS. However, whether M1-like TAM in melanoma can induce local HEV formation in tumors remains unknown. Our previous study showed that HIF-1α expression was up-regulated in Mɸ under hypoxia in vitro, and it was transformed into an M1-like phenotype, secreting large amounts of TNF-α. And the injection of hypoxic Mɸ into the tumor-site of Mɸ-cleared mouse promoted the formation of melanoma HEV and increased the number of TILs. Based on these results we speculated that under early hypoxic conditions of melanoma,TAM up-regulated HIF-1α expression and was differentiated into M1-like TNF-αhiMHC-IIhiTAM, which could activate TNF-α-TNFR pathway in tumor stromal vascular endothelial cells (VEC). The VECs gained the phenotype and function of HEV and recruited more TILs,which inhibited the progression of tumor. Therefore, melanoma samples from patients and mice models will be investigated to verify the hypothesis and reveal its underlying mechanism, thus providing new ideas for melanoma immunotherapy by targeting M1-like TAM.