Authors: Ruffin, Ayana T.; Cillo, Anthony R.; Tabib, Tracy; Liu, Angen; Onkar, Sayali; Kunning, Sheryl R.; Lampenfeld, Caleb; Atiya, Huda I.; Abecassis, Irina; Kürten, Cornelius H. L.; Qi, Zengbiao; Soose, Ryan; Duvvuri, Umamaheswar; Kim, Seungwon; Oesterrich, Steffi; Lafyatis, Robert; Coffman, Lan G.; Ferris, Robert L.; Vignali, Dario A. A.; Bruno, Tullia C.
Issue: Nat Commun. 2021 Jun 7;12(1):3349.
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.