Frontiers in Immunology (Mar 2021)

Tertiary Lymphoid Structure-B Cells Narrow Regulatory T Cells Impact in Lung Cancer Patients

  • Claire Germain,
  • Claire Germain,
  • Claire Germain,
  • Claire Germain,
  • Claire Germain,
  • Priyanka Devi-Marulkar,
  • Priyanka Devi-Marulkar,
  • Priyanka Devi-Marulkar,
  • Samantha Knockaert,
  • Samantha Knockaert,
  • Samantha Knockaert,
  • Jérôme Biton,
  • Jérôme Biton,
  • Jérôme Biton,
  • Hélène Kaplon,
  • Hélène Kaplon,
  • Hélène Kaplon,
  • Laïla Letaïef,
  • Laïla Letaïef,
  • Laïla Letaïef,
  • Laïla Letaïef,
  • Laïla Letaïef,
  • Jérémy Goc,
  • Jérémy Goc,
  • Jérémy Goc,
  • Agathe Seguin-Givelet,
  • Agathe Seguin-Givelet,
  • Agathe Seguin-Givelet,
  • Dominique Gossot,
  • Dominique Gossot,
  • Nicolas Girard,
  • Pierre Validire,
  • Pierre Validire,
  • Marine Lefèvre,
  • Marine Lefèvre,
  • Marine Lefèvre,
  • Diane Damotte,
  • Diane Damotte,
  • Diane Damotte,
  • Diane Damotte,
  • Marco Alifano,
  • Marco Alifano,
  • Marco Alifano,
  • Marco Alifano,
  • François M. Lemoine,
  • François M. Lemoine,
  • Keith E. Steele,
  • Jean-Luc Teillaud,
  • Jean-Luc Teillaud,
  • Jean-Luc Teillaud,
  • Jean-Luc Teillaud,
  • Jean-Luc Teillaud,
  • Scott A. Hammond,
  • Marie-Caroline Dieu-Nosjean,
  • Marie-Caroline Dieu-Nosjean,
  • Marie-Caroline Dieu-Nosjean,
  • Marie-Caroline Dieu-Nosjean,
  • Marie-Caroline Dieu-Nosjean

DOI
https://doi.org/10.3389/fimmu.2021.626776
Journal volume & issue
Vol. 12

Abstract

Read online

The presence of tertiary lymphoid structures (TLS) in the tumor microenvironment is associated with better clinical outcome in many cancers. In non-small cell lung cancer (NSCLC), we have previously showed that a high density of B cells within TLS (TLS-B cells) is positively correlated with tumor antigen-specific antibody responses and increased intratumor CD4+ T cell clonality. Here, we investigated the relationship between the presence of TLS-B cells and CD4+ T cell profile in NSCLC patients. The expression of immune-related genes and proteins on B cells and CD4+ T cells was analyzed according to their relationship to TLS-B density in a prospective cohort of 56 NSCLC patients. We observed that tumor-infiltrating T cells showed marked differences according to TLS-B cell presence, with higher percentages of naïve, central-memory, and activated CD4+ T cells and lower percentages of both immune checkpoint (ICP)-expressing CD4+ T cells and regulatory T cells (Tregs) in the TLS-Bhigh tumors. A retrospective study of 538 untreated NSCLC patients showed that high TLS-B cell density was even able to counterbalance the deleterious impact of high Treg density on patient survival, and that TLS-Bhigh Treglow patients had the best clinical outcomes. Overall, the correlation between the density of TLS-Bhigh tumors with early differentiated, activated and non-regulatory CD4+ T cell cells suggest that B cells may play a central role in determining protective T cell responses in NSCLC patients.

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