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B cell signatures and tertiary lymphoid structures contribute to outcome in head and neck squamous cell carcinoma

Author

Listed:
  • Ayana T. Ruffin

    (University of Pittsburgh
    University of Pittsburgh
    University of Pittsburgh School of Medicine
    Hillman Cancer Center)

  • Anthony R. Cillo

    (University of Pittsburgh
    University of Pittsburgh
    Hillman Cancer Center)

  • Tracy Tabib

    (University of Pittsburgh)

  • Angen Liu

    (University of Pittsburgh)

  • Sayali Onkar

    (University of Pittsburgh
    University of Pittsburgh
    University of Pittsburgh School of Medicine
    Hillman Cancer Center)

  • Sheryl R. Kunning

    (University of Pittsburgh
    University of Pittsburgh
    Hillman Cancer Center)

  • Caleb Lampenfeld

    (University of Pittsburgh
    University of Pittsburgh
    Hillman Cancer Center)

  • Huda I. Atiya

    (Hillman Cancer Center
    Hillman Cancer Center)

  • Irina Abecassis

    (University of Pittsburgh
    University of Pittsburgh
    Hillman Cancer Center)

  • Cornelius H. L. Kürten

    (University Duisburg-Essen)

  • Zengbiao Qi

    (University of Pittsburgh)

  • Ryan Soose

    (University of Pittsburgh)

  • Umamaheswar Duvvuri

    (Hillman Cancer Center
    University of Pittsburgh)

  • Seungwon Kim

    (University of Pittsburgh)

  • Steffi Oesterrich

    (Hillman Cancer Center
    University of Pittsburgh
    University of Pittsburgh)

  • Robert Lafyatis

    (University of Pittsburgh
    University of Pittsburgh)

  • Lan G. Coffman

    (Hillman Cancer Center
    Hillman Cancer Center)

  • Robert L. Ferris

    (University of Pittsburgh
    University of Pittsburgh
    Hillman Cancer Center
    University of Pittsburgh)

  • Dario A. A. Vignali

    (University of Pittsburgh
    University of Pittsburgh
    Hillman Cancer Center
    UPMC Hillman Cancer Center)

  • Tullia C. Bruno

    (University of Pittsburgh
    University of Pittsburgh
    Hillman Cancer Center
    UPMC Hillman Cancer Center)

Abstract

Current immunotherapy paradigms aim to reinvigorate CD8+ T cells, but the contribution of humoral immunity to antitumor immunity remains understudied. Here, we demonstrate that in head and neck squamous cell carcinoma (HNSCC) caused by human papillomavirus infection (HPV+), patients have transcriptional signatures of germinal center (GC) tumor infiltrating B cells (TIL-Bs) and spatial organization of immune cells consistent with tertiary lymphoid structures (TLS) with GCs, both of which correlate with favorable outcome. GC TIL-Bs in HPV+ HNSCC are characterized by distinct waves of gene expression consistent with dark zone, light zone and a transitional state of GC B cells. Semaphorin 4a expression is enhanced on GC TIL-Bs present in TLS of HPV+ HNSCC and during the differentiation of TIL-Bs. Our study suggests that therapeutics to enhance TIL-B responses in HNSCC should be prioritized in future studies to determine if they can complement current T cell mediated immunotherapies.

Suggested Citation

  • Ayana T. Ruffin & Anthony R. Cillo & Tracy Tabib & Angen Liu & Sayali Onkar & Sheryl R. Kunning & Caleb Lampenfeld & Huda I. Atiya & Irina Abecassis & Cornelius H. L. Kürten & Zengbiao Qi & Ryan Soose, 2021. "B cell signatures and tertiary lymphoid structures contribute to outcome in head and neck squamous cell carcinoma," Nature Communications, Nature, vol. 12(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-23355-x
    DOI: 10.1038/s41467-021-23355-x
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