Chang Mark J, Stamos Daniel B, Urtis Cetin, Bowers Nathan L, Schmalz Lauren M, Deyo Logan J, Porebski Martin F, Jabir Abdur Rahman, Bunch Paul M, Lycan Thomas W, Buchanan Doerfler Laura, Patwa Hafiz S, Waltonen Joshua D, Sullivan Christopher A, Browne J Dale, Zhang Wei, Porosnicu Mercedes
Department of Internal Medicine, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
Center for Cancer Genomics and Precision Oncology, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
Cancers (Basel). 2025 Mar 31;17(7):1172. doi: 10.3390/cancers17071172.
BACKGROUND/OBJECTIVES: Cutaneous squamous cell carcinoma (cSCC) harbors one of the most mutated genomes. There are limited data on the genomic profile and its predictive potential for response to immunotherapy with PD-1 inhibitors in cSCC.
This study retrospectively reviewed cSCC patients treated with PD-1 inhibitor monotherapy at a single institution. Clinical characteristics, treatment outcomes, PD-L1 expression, tumor mutation burden (TMB), and genomic profile in tumor and blood were analyzed. Logistic regression and a support vector classifier were used to validate identified biomarkers of significance.
Twenty-five patients were evaluable for response and had genomics tested in tumor and/or blood. Of the total, 80% of patients achieved an objective response: 40% complete response (CR), 32% partial response (PR) for more than 6 months, and 8% stable disease (SD) for more than 1 year; 20% of patients progressed on treatment. With a median follow-up of 21 months, progression-free survival (PFS) was 28 months in responders vs. 3 months in non-responders ( = 0.00001). Median PD-L1 was 25% in responders vs. 10% in non-responders ( = 0.39). There was no difference in median TMB between responders and non-responders. Eight gene mutations were significantly more frequent in non-responders than in responders: ( = 0.005), ( = 0.033), ( = 0.033), ( = 0.038), ( = 0.016), (0.033), ( = 0.016), and ( = 0.033). A support vector model of these genes classified responders and non-responders with an accuracy of 0.88 in the training data and 1.0 in the testing data.
PD-1 inhibitor monotherapy produces an impressive response. Eight gene mutations were significantly more frequent in non-responders. PD-L1 and TMB were inconclusive in predicting treatment response to anti-PD-L1.
背景/目的：皮肤鳞状细胞癌（cSCC）具有突变最多的基因组之一。关于cSCC的基因组概况及其对PD-1抑制剂免疫治疗反应的预测潜力的数据有限。
本研究回顾性分析了在单一机构接受PD-1抑制剂单药治疗的cSCC患者。分析了临床特征、治疗结果、PD-L1表达、肿瘤突变负荷（TMB）以及肿瘤和血液中的基因组概况。使用逻辑回归和支持向量分类器来验证已确定的具有显著意义的生物标志物。
25例患者可评估反应，并对肿瘤和/或血液进行了基因组检测。总体而言，80%的患者获得了客观反应：40%完全缓解（CR），32%部分缓解（PR）超过6个月，8%疾病稳定（SD）超过1年；20%的患者在治疗中病情进展。中位随访21个月，反应者的无进展生存期（PFS）为28个月，无反应者为3个月（P = 0.00001）。反应者的中位PD-L1为25%，无反应者为10%（P = 0.39）。反应者和无反应者的中位TMB无差异。8种基因突变在无反应者中比在反应者中显著更频繁：（P = 0.005），（P = 0.033），（P = 0.033），（P = 0.038），（P = 0.016），（P = 0.033），（P = 0.016），以及（P = 0.033）。这些基因的支持向量模型在训练数据中对反应者和无反应者的分类准确率为0.88，在测试数据中为1.0。
PD-1抑制剂单药治疗产生了令人印象深刻的反应。8种基因突变在无反应者中显著更频繁。PD-L1和TMB对于预测抗PD-L1治疗反应尚无定论。
