近日，美国国立卫生研究院Andrea Lisco团队实现了通过恢复T细胞受体信号传导来缓解鳞状细胞癌。相关论文于2025年7月31日发表在《新英格兰医学杂志》上。

皮肤鳞状细胞癌（SCC）主要由紫外线辐射介导的致癌作用引起，而β型人乳头瘤病毒（β-HPV）被认为仅是一种促进因素，对于皮肤SCC的维持并非必需。研究组描述了一名女性患者，她同时患有良性和恶性HPV相关疾病，包括复发性、不可切除的侵袭性皮肤SCC，该SCC伴有β-HPV19基因组整合，且患者存在T细胞受体（TCR）信号转导所需适配器ZAP70的种系致病突变。

通过异基因造血细胞移植恢复TCR信号传导的完整性，使所有HPV相关疾病得到缓解，从而揭示了在适应性T细胞反应缺陷的宿主中，β-HPV在皮肤癌发生中的直接作用。

附：英文原文

Title: Resolution of Squamous-Cell Carcinoma by Restoring T-Cell Receptor Signaling

Author: Peiying Ye, Jenna R.E. Bergerson, Isaac Brownell, Gabriel J. Starrett, Roshini S. Abraham, Megan V. Anderson, Triscia Martin, Derek MacMath, Hye Sun Kuehn, Jyothi Padiadpu, Siqi Zhao, Sergio D. Rosenzweig, Roxane Tussiwand, Warren J. Leonard, Stefania Pittaluga, Mark Raffeld, Danielle E. Arnold, Andrea Lisco

Issue&Volume: 2025-07-31

Abstract: Cutaneous squamous-cell carcinoma (SCC) is primarily caused by oncogenesis mediated by ultraviolet radiation, and β-human papillomavirus (β-HPV) is believed to be a mere facilitator that is dispensable for the maintenance of cutaneous SCC. Here, we describe a woman with benign and malignant HPV-related diseases that include a recurrent, unresectable, invasive cutaneous SCC with β-HPV19 genomic integration in the context of germline pathogenic mutations in ZAP70, an adapter required for T-cell receptor (TCR) signal transduction. Restoration of the integrity of TCR signaling by allogeneic hematopoietic-cell transplantation led to the resolution of all HPV-related diseases, thereby revealing a direct role of β-HPV in skin carcinogenesis in hosts with defective adaptive T-cell responses.

DOI: NJ202507313930510

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2502114