Department of Surgery, Austin Health, Heidelberg, VIC, Australia.
Olivia Newton-John Cancer Research Institute, School of Cancer Medicine, La Trobe University, Heidelberg, VIC, Australia.
Front Immunol. 2024 Oct 31;15:1474663. doi: 10.3389/fimmu.2024.1474663. eCollection 2024.
We report the partial regression of metastatic squamous cell carcinoma (SCC) after reduction of long-term azathioprine therapy while awaiting surgery. The patient was a 69-year-old man with a history of kidney transplantation. Moderately differentiated SCC arising in the anterior neck was initially diagnosed, followed later by poorly differentiated SCC metastases to cervical lymph nodes. Lymph node clearance was performed 28 days after a reduction in azathioprine dosage. The palpable lymph node lesion had noticeably decreased in size at the time of surgery, and subsequent histology only detected 7mm and 0.2mm deposits of poorly differentiated SCC in 2 of 5 level I nodes, and a further 10 reactive nodes from levels II and III. One positive level I and another benign level II/III node, demonstrated necrosis, histiocytic infiltration and fibrosis, interpreted as features of regression. Hence, we investigated the role of immune cells in the partial regression of metastatic SCC after reduction of long-term azathioprine therapy while awaiting surgery.
Multispectral immunohistochemistry using custom markers was performed on regions of interest of excised cervical lymph nodes, encompassing the entire SCC deposit and the surrounding adjacent stroma to quantify to number and types of immune cells present.
Multispectral immunohistochemistry revealed the heavy infiltration of activated T cells in the tumour, as well as PD-L1+ antigen-presenting cells in the surrounding adjacent stroma, suggesting an immunologically mediated partial regression.
We hypothesize that this reaction was triggered by azathioprine dose reduction. Dose modification of long-term immunosuppressive medications in patients with a transplantation history who later develop SCCs warrants further investigation.
我们报告了一例长期接受硫唑嘌呤治疗的转移性鳞状细胞癌(SCC)患者,在等待手术期间,由于减少硫唑嘌呤剂量而部分消退。患者为 69 岁男性,有肾移植病史。最初诊断为颈部前部的中分化 SCC,随后出现低分化 SCC 颈部淋巴结转移。在减少硫唑嘌呤剂量 28 天后进行了淋巴结清扫。手术时,可触及的淋巴结病变明显缩小,随后的组织学检查仅在 5 个 I 级淋巴结中的 2 个中发现 7mm 和 0.2mm 的低分化 SCC 沉积,另外 10 个来自 II 级和 III 级的反应性淋巴结。一个阳性的 I 级和另一个良性的 II/III 级淋巴结表现为坏死、组织细胞浸润和纤维化,被解释为消退的特征。因此,我们研究了在等待手术期间减少长期硫唑嘌呤治疗后,免疫细胞在转移性 SCC 部分消退中的作用。
对切除的颈部淋巴结进行多光谱免疫组织化学分析,使用定制标记物对感兴趣区域进行分析,包括整个 SCC 沉积物和周围相邻的基质,以定量分析存在的免疫细胞数量和类型。
多光谱免疫组织化学显示肿瘤中活化 T 细胞的大量浸润,以及周围相邻基质中 PD-L1+抗原呈递细胞,提示免疫介导的部分消退。
我们假设这种反应是由硫唑嘌呤剂量减少引起的。对有移植病史且后来发生 SCC 的患者进行长期免疫抑制药物剂量调整值得进一步研究。