病例报告：PD-L1 阴性、TMB 低、KEAP1/STK11 共突变转移性 NSCLC 假性进展的免疫反应特征。
Case report: Immune response characterization of a pseudoprogression in a PD-L1-negative, TMB-low, KEAP1/STK11 co-mutated metastatic NSCLC.
发表日期：2024
作者：
Nicolas Roussot, Marion Thibaudin, Jean-David Fumet, Susy Daumoine, Léa Hampe, Cédric Rébé, Emeric Limagne, Aurélie Lagrange, Victor Herreros, Julie Lecuelle, Hugo Mananet, Alis Ilie, David Rageot, Romain Boidot, Vincent Goussot, Anthony Comte, Pierre Jacob, Françoise Beltjens, Anthony Bergeron, Céline Charon-Barra, Laurent Arnould, Valentin Derangère, Sylvain Ladoire, Caroline Truntzer, François Ghiringhelli
来源：
Frontiers in Immunology
摘要：
一名 PD-L1 阴性、TMB 低、KEAP1/STK11 共突变的转移性非小细胞肺癌 (NSCLC) 患者在开始化疗作为转移性疾病一线治疗后 3 个月时出现多部位放射学进展。放射学进展后，在未接受治疗的情况下，患者出现自发病灶缩小，并进一步实现了长时间的完全缓解。在基线和假进展时收集的基因组和转录组数据使我们能够从生物学角度描述这种罕见的反应模式。我们观察到针对肿瘤特异性新抗原（TNA）的肿瘤特异性 T 细胞反应的存在。还观察到化学免疫治疗后内源性逆转录病毒 (ERV) 的表达，同时还观察到具有 I 型 IFN 信号传导和 CXCR3 相关趋化因子产生的抗病毒样先天免疫反应的生物学特征。这是化学免疫疗法下 NSCLC 假性进展的第一个生物学特征，随后在 PD-L1 阴性、TMB 低、KEAP1/STK11 共突变 NSCLC 中出现长期完全缓解。这些临床和生物学数据强调，即使患者对免疫检查点抑制剂具有多种耐药性，也可能引发针对肿瘤新抗原的肿瘤特异性免疫反应，从而彻底根除肿瘤，并可能产生疫苗免疫反应。版权所有 © 2024 Roussot, Thibaudin 、Fumet、Daumoine、Hampe、Rébé、Limagne、Lagrange、Herreros、Lecuelle、Mananet、Ilie、Rageot、Boidot、Goussot、Comte、Jacob、Beltjens、Bergeron、Charon-Barra、Arnould、Derangère、Ladoire、Truntzer 和 Ghiringhelli。
A patient with a PD-L1-negative, TMB-low, KEAP1/STK11 co-mutated metastatic non-small cell lung cancer (NSCLC) experienced a multisite radiological progression at 3 months after initiation of chemoimmunotherapy as first-line treatment for metastatic disease. After the radiological progression, while she was not undergoing treatment, the patient had spontaneous lesions shrinkage and further achieved a prolonged complete response. Genomic and transcriptomic data collected at baseline and at the time of pseudoprogression allowed us to biologically characterize this rare response pattern. We observed the presence of a tumor-specific T-cell response against tumor-specific neoantigens (TNAs). Endogenous retroviruses (ERVs) expression following chemoimmunotherapy was also observed, concurrent with biological features of an anti-viral-like innate immune response with type I IFN signaling and production of CXCR3-associated chemokines. This is the first biological characterization of a NSCLC pseudoprogression under chemoimmunotherapy followed by a prolonged complete response in a PD-L1-negative, TMB-low, KEAP1/STK11 co-mutated NSCLC. These clinical and biological data underline that even patients with multiple factors of resistance to immune checkpoint inhibitors could trigger a tumor-specific immune response to tumor neoantigen, leading to complete eradication of the tumor and probably a vaccinal immune response.Copyright © 2024 Roussot, Thibaudin, Fumet, Daumoine, Hampe, Rébé, Limagne, Lagrange, Herreros, Lecuelle, Mananet, Ilie, Rageot, Boidot, Goussot, Comte, Jacob, Beltjens, Bergeron, Charon-Barra, Arnould, Derangère, Ladoire, Truntzer and Ghiringhelli.