Nahm William J, Sakunchotpanit Goranit, Nambudiri Vinod E
New York University Grossman School of Medicine, New York, NY, USA.
Department of Dermatology, Brigham and Women's Hospital, 117 Western Avenue, Boston, MA, 02163, USA.
Am J Clin Dermatol. 2025 Apr 3. doi: 10.1007/s40257-025-00943-x.
Radiation therapy (RT) is a crucial modality in cancer treatment, functioning through direct DNA damage and immune stimulation. However, RT's effects extend beyond targeted cells, influencing neighboring cells through the bystander effect (ByE) and distant sites via the abscopal effect (AbE). The AbE, first described by Mole in 1953, encompasses biological reactions at sites distant from the irradiation field. While RT can enhance antitumor immune responses, it may also contribute to an immunosuppressive microenvironment. To address this limitation, combining RT with immune checkpoint inhibitors (ICIs) has gained renewed interest, aiming to amplify antitumor immune responses. Evidence of AbEs has been observed in various metastatic or advanced cutaneous cancers, including melanoma, basal cell carcinoma, cutaneous lymphoma, Merkel cell carcinoma, and cutaneous squamous cell carcinoma. Clinical studies suggest combining RT with ICIs targeting CTLA-4 and PD-1/PD-L1 may enhance AbE incidence in these cancers. This review primarily explores the current understanding of AbEs in skin cancers, briefly acknowledging the ByE focusing on combining RT with immunomodulation. It focuses on proposed mechanisms, preclinical and clinical evidence, challenges in clinical translation, and future directions for harnessing AbEs in managing advanced skin malignancies. Alternative modalities for inducing abscopal-like responses are also explored. While promising, challenges remain in consistently reproducing AbEs in clinical practice, necessitating further research to optimize treatment combinations, timing, and patient selection.
放射治疗（RT）是癌症治疗中的一种关键方式，通过直接损伤DNA和刺激免疫发挥作用。然而，RT的影响不仅限于靶向细胞，还会通过旁观者效应（ByE）影响邻近细胞，并通过远隔效应（AbE）影响远处部位。远隔效应由莫尔于1953年首次描述，包括照射野以外部位的生物反应。虽然RT可以增强抗肿瘤免疫反应，但它也可能导致免疫抑制微环境。为了解决这一局限性，将RT与免疫检查点抑制剂（ICIs）联合使用重新引起了人们的兴趣，旨在增强抗肿瘤免疫反应。在各种转移性或晚期皮肤癌中都观察到了远隔效应的证据，包括黑色素瘤、基底细胞癌、皮肤淋巴瘤、默克尔细胞癌和皮肤鳞状细胞癌。临床研究表明，将RT与靶向CTLA-4和PD-1/PD-L1的ICIs联合使用可能会增加这些癌症中远隔效应的发生率。本综述主要探讨目前对皮肤癌中远隔效应的理解，简要提及旁观者效应，并着重于RT与免疫调节的联合应用。它关注提出的机制、临床前和临床证据、临床转化中的挑战以及利用远隔效应治疗晚期皮肤恶性肿瘤的未来方向。还探讨了诱导类似远隔效应的替代方式。虽然前景广阔，但在临床实践中持续重现远隔效应仍存在挑战，需要进一步研究以优化治疗组合、时机和患者选择。
