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中华损伤与修复杂志(电子版) ›› 2026, Vol. 21 ›› Issue (03) : 236 -240. doi: 10.3877/cma.j.issn.1673-9450.2026.03.011

综述

泛凋亡调控网络在黑色素瘤免疫微环境重塑与耐药逆转中作用的研究进展
王福军1, 陈泳键2, 王子强3, 程新蓓4, 杨荣华3,()   
  1. 1 161006 齐齐哈尔医学院基础医学院
    2 524023 湛江,广东医科大学第一临床医学院
    3 510180 广州,华南理工大学附属第二医院烧伤整形美容与创面修复科
    4 161006 齐齐哈尔医学院护理学院
  • 收稿日期:2026-02-22 出版日期:2026-06-01
  • 通信作者: 杨荣华
  • 基金资助:
    国家自然科学基金面上项目(82272276); 广东省基础与应用基础研究基金(2022A1515012160,2024A1515010477); 广州市校(院)企联合资助重点项目(SL2024A03J01405)

Research progress on the role of regulatory network of PANoptosis in remodeling the immune microenvironment and reversing drug resistance in melanoma

Fujun Wang1, Yongjian Chen2, Ziqiang Wang3, Xinbei Cheng4, Ronghua Yang3,()   

  1. 1 School of Basic Medical Sciences, Qiqihar Medical University, Qiqihar 161006, China
    2 First Clinical Medical College, Guangdong Medical University, Zhanjiang 524023, China
    3 Department of Burn and Plastic Surgery, the Second Affiliated Hospital of South China University of Technology, Guangzhou 510180, China
    4 School of Nursing, Qiqihar Medical University, Qiqihar 161006, China
  • Received:2026-02-22 Published:2026-06-01
  • Corresponding author: Ronghua Yang
引用本文:

王福军, 陈泳键, 王子强, 程新蓓, 杨荣华. 泛凋亡调控网络在黑色素瘤免疫微环境重塑与耐药逆转中作用的研究进展[J/OL]. 中华损伤与修复杂志(电子版), 2026, 21(03): 236-240.

Fujun Wang, Yongjian Chen, Ziqiang Wang, Xinbei Cheng, Ronghua Yang. Research progress on the role of regulatory network of PANoptosis in remodeling the immune microenvironment and reversing drug resistance in melanoma[J/OL]. Chinese Journal of Injury Repair and Wound Healing(Electronic Edition), 2026, 21(03): 236-240.

恶性黑色素瘤常对靶向药物及免疫检查点阻断产生耐药,其核心在于恶性细胞发生调控性细胞死亡的能力受损及免疫抑制微环境占主导,导致单纯靶向线粒体凋亡疗效有限。泛凋亡整合焦亡、凋亡与坏死性凋亡过程,可提升肿瘤细胞清除率,促进三磷酸腺苷(ATP)和抗原释放,增强炎症与干扰素信号,从而改善抗原呈递和效应细胞募集,促进免疫治疗应答。然而,缺氧、酸性环境、自噬增强及表观遗传沉默等因素可减缓泛凋亡启动与放大。该文对泛凋亡分子结构及其对黑色素瘤免疫微环境的影响和相关耐药机制进行综述,提出B细胞淋巴瘤2相关蛋白A1(BCL2A1)可能通过抑制泛凋亡复合体发挥负调控作用,并探讨靶向BCL2A1与泛凋亡诱导剂联合应用的研究方向,为逆转黑色素瘤耐药提供参考。

Malignant melanoma frequently develops resistance to targeted agents and immune checkpoint blockade. The core reason lies in the impaired ability of malignant cells to undergo regulated cell death, along with the dominance of an immunosuppressive microenvironment, which limits the efficacy of solely targeting mitochondrial apoptosis. PANapoptosis integrates pyroptosis, apoptosis, and necroptosis, thereby enhancing tumor cell clearance, promoting the release of adenosine triphosphate (ATP) and antigens, and amplifying inflammatory and interferon signaling. These effects improve antigen presentation and effector immune cell recruitment, ultimately enhancing responses to immunotherapy. However, factors such as hypoxia, acidic environment, enhanced autophagy, and epigenetic silencing can hinder the initiation and amplification of PANapoptosis. This review summarizes the molecular architecture of PANapoptosis and its impact on the immune microenvironment of melanoma, as well as relevant resistance mechanisms, proposes that B-cell lymphoma 2-related protein A1 (BCL2A1) may play a negative regulatory role by inhibiting the PANapoptotic complex, and explores the potential of combining BCL2A1 targeting with PANapoptosis inducers as a direction for overcoming therapeutic resistance in melanoma.

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