Department of Oral Medicine, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China.
Department of Oral and Maxillofacial Surgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China.
J Oncol Pharm Pract. 2024 Jan;30(1):228-234. doi: 10.1177/10781552231203723. Epub 2023 Oct 11.
Camrelizumab is a novel anti-programed cell death-1 (PD-1) antibody that has been investigated for the treatment of various malignancies. Increasing immune-related adverse events have been reported in clinical practice, with CD4+ T-cell-mediated-reactive cutaneous capillary endothelial proliferation being the most common. Camrelizumab-induced oral lichenoid reaction (OLR) appears to be a rare adverse effect compared with other anti-PD therapies induced OLR, with the main pathogenesis of activated CD8+ T cells mediating autoimmune reactions. Herein, we report a rare case of camrelizumab-induced OLR and a possible pathogenic mechanism of subepithelial CD4+ T-cell infiltration.
A 57-year-old male patient, who was diagnosed with metastatic esophageal squamous cell carcinoma three years prior, presented with a two-month history of oral erosion that developed while under camrelizumab therapy. Diffuse erythematous and erosive lesions surrounded by bilateral white lesions on the buccal mucosa were detected in his physical examination. Hematoxylin and eosin staining of the lesions revealed the presence of basal keratinocyte degeneration and band-like subepithelial T-cell infiltration. The immunostaining for CD4 on T-cell was positive, while CD8 were sporadically positive. Flow cytometry showed a gradual increase in the CD4+ T-cell proportion in the peripheral blood, with the CD8+ T-cell percentage almost unchanged and in the normal range. We obtained a score of 6 based on the Naranjo algorithm, which means a probable adverse drug reaction.
The patient exhibited notable improvement after two weeks of treatment with topical glucocorticoid without regulating his immunotherapy, and remained in stable condition in the follow-up.
This case may offer new insight to clinicians on the pathogenesis of anti-PD-1-induced OLR. More critically, it may provide some ideas for a more precise anti-PD therapy or corresponding combination therapy for patients becoming resistant to immunotherapy due to exhausted CD4+ T-cell responses in the tumor microenvironment.
卡瑞利珠单抗是一种新型的抗程序性细胞死亡蛋白-1（PD-1）抗体，已被研究用于治疗各种恶性肿瘤。在临床实践中，越来越多的免疫相关不良反应被报道，其中以 CD4+T 细胞介导的反应性皮肤毛细血管内皮增生最为常见。与其他抗 PD 治疗引起的口腔苔藓样反应（OLR）相比，卡瑞利珠单抗引起的口腔苔藓样反应（OLR）似乎是一种罕见的不良反应，其主要发病机制是激活的 CD8+T 细胞介导的自身免疫反应。在此，我们报告一例卡瑞利珠单抗诱导的 OLR 病例，并探讨了亚上皮 CD4+T 细胞浸润的可能发病机制。
一名 57 岁男性患者，三年前被诊断为转移性食管鳞状细胞癌，在接受卡瑞利珠单抗治疗期间出现了两个月的口腔糜烂病史。体格检查发现颊黏膜双侧白色病变环绕弥漫性红斑和糜烂性病变。病变的苏木精-伊红染色显示基底角质形成细胞变性和带状亚上皮 T 细胞浸润。T 细胞 CD4 的免疫染色阳性，而 CD8 则呈散在阳性。流式细胞术显示外周血中 CD4+T 细胞比例逐渐增加，CD8+T 细胞百分比几乎不变且处于正常范围。根据 Naranjo 算法，我们获得了 6 分，这意味着可能存在药物不良反应。
患者在接受两周的局部糖皮质激素治疗后，症状明显改善，且未调整免疫治疗，在随访中情况稳定。
该病例可能为临床医生提供了关于抗 PD-1 诱导的 OLR 发病机制的新见解。更重要的是，它可能为因肿瘤微环境中 CD4+T 细胞反应耗尽而对免疫治疗产生耐药的患者提供了更精确的抗 PD 治疗或相应的联合治疗思路。
