ArticlemedRxiv : the preprint server for health sciences2025
Napsin A-specific T cell clonotypes are associated with improved clinical outcomes in patients receiving checkpoint immunotherapy for metastatic non-small cell lung cancer.
Article in medRxiv : the preprint server for health sciences, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: Napsin A is normally expressed in human lung pneumocytes and is a highly expressed cancer antigen in lung adenocarcinoma. We examined whether T cells specific for Napsin A may play a role in immune checkpoint inhibitor (ICI)-mediated responses. We utilized bulk TCR repertoire data to assess whether the presence of Napsin A-specific clonotypes in the peripheral blood was associated with improved clinical responses to ICI. Methods: Patients with metastatic non-small cell lung cancer (NSCLC) receiving anti-PD-(L)1 (alone or in combination) were enrolled at Fred Hutchinson Cancer Center and Stanford University Medical Center (n=62; histology of adenocarcinoma n=48, squamous n=9, NSCLC/other n=5). Peripheral blood mononuclear cells (PBMC) were collected for genomic DNA isolation pre- and post-treatment (range 3 weeks - 3 months). TCRβ was bulk sequenced via the immunoSEQ platform (Adaptive Biotechnologies). Napsin A-specific TCRβ sequences were identified from publicly available data and their frequencies were quantified in each patient sample. We examined whether overall survival (OS) and progression-free survival (PFS) outcomes differed in patients with or without detectable Napsin A-specific TCRs (herein Napsin TCRs). We used Cox proportional hazards regression to assess the association between detectable Napsin TCRs and PFS or OS in univariable and multivariable analyses. Results: Napsin TCRs were detectable in the blood in a large fraction of our cohort (n=25/62 [40%] [pre-treatment; n=21/42 [50%] post-treatment). Patients with detectable Napsin TCRs had a significant improvement in OS compared to patients without these TCRs (median OS 45.4 vs 14.8 months, p=0.0043 pre-treatment; median OS 55.4 vs 18.9 months, p=0.0066 post-treatment). Among 27 Conclusions: Napsin TCRs are frequently detected in patients with NSCLC and are associated with improved OS in patients with NSCLC receiving ICI. KEY MESSAGES:
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