Eshaq Abdulaziz M, Flanagan Thomas W, Ba Abbad Abdulqader A, Makarem Zain Alabden A, Bokir Mohammed S, Alasheq Ahmed K, Al Asheikh Sara A, Almashhor Abdullah M, Binyamani Faroq, Al-Amoudi Waleed A, Bawzir Abdulaziz S, Haikel Youssef, Megahed Mossad, Hassan Mohamed
Department of Epidemiology and Biostatstics, Milken Institute School of Public Health, George Washington University Washington, Washington, DC 20052, USA.
Research Laboratory of Surgery-Oncology, Department of Surgery, Tulane University School of Medicine, New Orleans, LA 70112, USA.
Int J Mol Sci. 2024 Dec 26;26(1):88. doi: 10.3390/ijms26010088.
Immunotherapy, particularly that based on blocking checkpoint proteins in many tumors, including melanoma, Merkel cell carcinoma, non-small cell lung cancer (NSCLC), triple-negative breast (TNB cancer), renal cancer, and gastrointestinal and endometrial neoplasms, is a therapeutic alternative to chemotherapy. Immune checkpoint inhibitor (ICI)-based therapies have the potential to target different pathways leading to the destruction of cancer cells. Although ICIs are an effective treatment strategy for patients with highly immune-infiltrated cancers, the development of different adverse effects including cutaneous adverse effects during and after the treatment with ICIs is common. ICI-associated cutaneous adverse effects include mostly inflammatory and bullous dermatoses, as well as severe cutaneous side reactions such as rash or inflammatory dermatitis encompassing erythema multiforme; lichenoid, eczematous, psoriasiform, and morbilliform lesions; and palmoplantar erythrodysesthesia. The development of immunotherapy-related adverse effects is a consequence of ICIs' unique molecular action that is mainly mediated by the activation of cytotoxic CD4/CD8 T cells. ICI-associated cutaneous disorders are the most prevalent effects induced in response to anti-programmed cell death 1 (PD-1), anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4), and anti-programmed cell death ligand 1 (PD-L1) agents. Herein, we will elucidate the mechanisms regulating the occurrence of cutaneous adverse effects following treatment with ICIs.
免疫疗法，尤其是基于阻断许多肿瘤（包括黑色素瘤、默克尔细胞癌、非小细胞肺癌（NSCLC）、三阴性乳腺癌（TNB癌）、肾癌以及胃肠道和子宫内膜肿瘤）中的检查点蛋白的免疫疗法，是化疗的一种治疗替代方案。基于免疫检查点抑制剂（ICI）的疗法有可能靶向导致癌细胞破坏的不同途径。尽管ICI对免疫高度浸润的癌症患者是一种有效的治疗策略，但在ICI治疗期间及之后出现包括皮肤不良反应在内的不同不良反应是很常见的。ICI相关的皮肤不良反应主要包括炎症性和大疱性皮肤病，以及严重的皮肤副作用，如皮疹或包括多形红斑的炎症性皮炎；苔藓样、湿疹样、银屑病样和麻疹样病变；以及掌跖红细胞感觉异常。免疫疗法相关不良反应的发生是ICI独特分子作用的结果，这种作用主要由细胞毒性CD4/CD8 T细胞的激活介导。ICI相关的皮肤疾病是对抗程序性细胞死亡1（PD-1）、抗细胞毒性T淋巴细胞相关抗原4（CTLA-4）和抗程序性细胞死亡配体1（PD-L1）药物产生的最常见反应。在此，我们将阐明ICI治疗后调节皮肤不良反应发生的机制。
