Case report: Immune response characterization of a pseudoprogression in a PD-L1-negative, TMB-low, co-mutated metastatic NSCLC.

Fiche publication

Date publication

août 2024

Journal

Frontiers in immunology

Auteurs

Membres identifiés du Cancéropôle Est :
Dr ARNOULD Laurent , Dr BOIDOT Romain , Pr GHIRINGHELLI François , Dr LADOIRE Sylvain , Mme TRUNTZER Caroline , Dr REBE Cédric , Dr LIMAGNE Emeric , Dr CHARON-BARRA Céline , Dr DERANGERE Valentin , Dr FUMET Jean-David , Dr THIBAUDIN Marion , Dr GOUSSOT Vincent

Tous les auteurs :
Roussot N, Thibaudin M, Fumet JD, Daumoine S, Hampe L, Rébé C, Limagne E, Lagrange A, Herreros V, Lecuelle J, Mananet H, Ilie A, Rageot D, Boidot R, Goussot V, Comte A, Jacob P, Beltjens F, Bergeron A, Charon-Barra C, Arnould L, Derangère V, Ladoire S, Truntzer C, Ghiringhelli F

Lien Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/39170614

Résumé

A patient with a PD-L1-negative, TMB-low, 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, 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.