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- Title
Case report: Immune response characterization of a pseudoprogression in a PD-L1-negative, TMB-low, KEAP1/STK11 co-mutated metastatic NSCLC.
- Authors
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, Franc¸ oise; Bergeron, Anthony; Charon-Barra, Céline
- Abstract
A patient with a PD-L1-negative, TMB-low, KEAP1/STK11 co-mutated metastatic non-small cell lung cancer (NSCLC) experienced amultisite 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.
- Subjects
NON-small-cell lung carcinoma; IMMUNE checkpoint inhibitors; ENDOGENOUS retroviruses; THERAPEUTICS; IMMUNE response
- Publication
Frontiers in Immunology, 2024, p1
- ISSN
1664-3224
- Publication type
Article
- DOI
10.3389/fimmu.2024.1437961