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Interplay between plasmacytoid dendritic cells and tumor-specific T cells in peripheral blood influences long-term survival in non-small cell lung carcinoma

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Abstract

Plasmacytoid dendritic cells (pDCs) represent a subset of antigen-presenting cells that play an ambivalent role in cancer immunity. Here, we investigated the clinical significance of circulating pDCs and their interaction with tumor-specific T cell responses in patients with non-small cell lung cancer (NSCLC, n = 126) . The relation between intratumoral pDC signature and immune checkpoint inhibitors efficacy was also evaluated. Patients with NSCLC had low level but activated phenotype pDC compared to healthy donors. In overall population, patients with high level of pDC (pDChigh) had improved overall survival (OS) compared to patients with pDClow, median OS 30.4 versus 20.7 months (P = 0.013). This clinical benefit was only observed in stage I to III patients, but not in metastatic disease. We showed that patients harboring pDChigh profile had high amount of Th1-diffentiation cytokine interleukin-12 (IL-12) in blood and had functional T cells directed against a broad range of tumor antigens. Furthermore, a high pDC signature in the tumor microenvironment was associated with improved clinical outcome in patients treated with anti-PD-(L)1 therapy. Overall, this study showed that circulating pDChigh is associated with long-term OS in NSCLC and highlighted the predictive value of intratumor pDC signature in the efficacy of immune checkpoint inhibitors.

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Acknowledgements

We thank all patients who contributed to this study. We thank all of the medical doctors and nurses, from oncologic department of University Hospital of Besançon and European Georges Pompidou hospital in Paris, for their contributions. The authors also thank the Biomonitoring platform (EFS, CIC-1431) for their technical support.

Funding

This work was supported by grants from, La Ligue Contre le Cancer Grand Est 2020, the Conseil Regional de Franche-Comte, INCa-PLBio-2018.

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Authors and Affiliations

  1. INSERM, EFS BFC, UMR1098, RIGHT Interactions Greffon-Hôte Tumeur/Ingénierie Cellulaire et Génique, Univ. Bourgogne Franche-Comté, 25000, Besançon, France

    Caroline Laheurte, Evan Seffar, Eléonore Gravelin, Adeline Renaudin, Laura Boullerot, Marine Malfroy, Amélie Marguier, Benoit Lecoester, Philippe Saas & Olivier Adotevi

  2. INSERM CIC-1431, Clinical Investigation Center in Biotherapy, Plateforme de Biomonitoring, 25000, Besançon, France

    Caroline Laheurte, Eléonore Gravelin, Adeline Renaudin, Laura Boullerot, Philippe Saas & Olivier Adotevi

  3. Platform of Transfer in Biological Oncology, Georges François Leclerc Cancer Center – UNICANCER, 1 rue du Professeur Marion, 21000, Dijon, France

    Julie Lecuelle, Caroline Truntzer & Francois Ghiringhelli

  4. UMR INSERM 1231, 7 Boulevard Jeanne d’Arc, 21000, Dijon, France

    Julie Lecuelle, Caroline Truntzer & Francois Ghiringhelli

  5. INSERM UMR938, Centre de Recherche Saint-Antoine (CRSA), 75012, Paris, France

    Béatrice Gaugler

  6. Service Oncologie médicale, University Hospital of Besançon, 25000, Besançon, France

    Olivier Adotevi

  7. INSERM UMR1098, RIGHT Institute, EFS Bourgogne Franche-Comté, 8, rue du Docteur JF-Xavier Girod, BP 1937, 25020, Besançon Cedex, France

    Olivier Adotevi

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  1. Caroline Laheurte
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  2. Evan Seffar
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Contributions

OA was involved in conceptualization and acquired the funding; OA, BG, PS and CL were responsible for methodology; CL, EG, AR, LB and MM acquired the data; CL, ES, AM, BL and OA carried out formal analysis and investigation; JL, CT, FG conducted RNA-Seq analysis. CL and OA wrote and prepared the original draft; FG, CL and OA wrote, reviewed and edited the manuscript; OA contributed to supervision.

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Correspondence to Olivier Adotevi.

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Laheurte, C., Seffar, E., Gravelin, E. et al. Interplay between plasmacytoid dendritic cells and tumor-specific T cells in peripheral blood influences long-term survival in non-small cell lung carcinoma. Cancer Immunol Immunother 72, 579–589 (2023). https://doi.org/10.1007/s00262-022-03271-9

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