B cell signatures and tertiary lymphoid structures contribute to outcome in head and neck squamous cell carcinoma
Ayana T. Ruffin, Anthony R. Cillo, Tracy Tabib, Angen Liu, Sayali Onkar, Sheryl Kunning, Caleb Lampenfeld, Huda I. Atiya, Irina Abécassis, Cornelius Kürten, Zengbiao Qi, Ryan J. Soose, Umamaheswar Duvvuri, Seungwon Kim, Steffi Oesterrich, Robert Lafyatis, Lan Coffman, Robert L. Ferris, Dario A.A. Vignali, Tullia C. Bruno
Abstract
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.