Frontiers in Immunology (Aug 2024)

Case report: Immune response characterization of a pseudoprogression in a PD-L1-negative, TMB-low, KEAP1/STK11 co-mutated metastatic NSCLC

  • Nicolas Roussot,
  • Nicolas Roussot,
  • Nicolas Roussot,
  • Nicolas Roussot,
  • Marion Thibaudin,
  • Marion Thibaudin,
  • Jean-David Fumet,
  • Jean-David Fumet,
  • Jean-David Fumet,
  • Jean-David Fumet,
  • Susy Daumoine,
  • Susy Daumoine,
  • Léa Hampe,
  • Léa Hampe,
  • Cédric Rébé,
  • Cédric Rébé,
  • Emeric Limagne,
  • Emeric Limagne,
  • Emeric Limagne,
  • Aurélie Lagrange,
  • Victor Herreros,
  • Julie Lecuelle,
  • Julie Lecuelle,
  • Hugo Mananet,
  • Hugo Mananet,
  • Alis Ilie,
  • Alis Ilie,
  • David Rageot,
  • David Rageot,
  • Romain Boidot,
  • Romain Boidot,
  • Vincent Goussot,
  • Anthony Comte,
  • Pierre Jacob,
  • Pierre Jacob,
  • Pierre Jacob,
  • Pierre Jacob,
  • Françoise Beltjens,
  • Anthony Bergeron,
  • Céline Charon-Barra,
  • Laurent Arnould,
  • Valentin Derangère,
  • Valentin Derangère,
  • Valentin Derangère,
  • Sylvain Ladoire,
  • Sylvain Ladoire,
  • Sylvain Ladoire,
  • Sylvain Ladoire,
  • Caroline Truntzer,
  • Caroline Truntzer,
  • François Ghiringhelli,
  • François Ghiringhelli,
  • François Ghiringhelli,
  • François Ghiringhelli

DOI
https://doi.org/10.3389/fimmu.2024.1437961
Journal volume & issue
Vol. 15

Abstract

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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.

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