AUTHOR=Roussot Nicolas , Thibaudin Marion , Fumet Jean-David , Daumoine Susy , Hampe Léa , Rébé Cédric , Limagne Emeric , Lagrange Aurélie , Herreros Victor , Lecuelle Julie , Mananet Hugo , Ilie Alis , Rageot David , Boidot Romain , Goussot Vincent , Comte Anthony , Jacob Pierre , Beltjens Françoise , Bergeron Anthony , Charon-Barra Céline , Arnould Laurent , Derangère Valentin , Ladoire Sylvain , Truntzer Caroline , Ghiringhelli François TITLE=Case report: Immune response characterization of a pseudoprogression in a PD-L1-negative, TMB-low, KEAP1/STK11 co-mutated metastatic NSCLC JOURNAL=Frontiers in Immunology VOLUME=15 YEAR=2024 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1437961 DOI=10.3389/fimmu.2024.1437961 ISSN=1664-3224 ABSTRACT=

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.