Department of Immunology, University of Pittsburgh, Pittsburgh, PA, USA.
Tumor Microenvironment Center, Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA, USA.
Nat Commun. 2021 Jun 7;12(1):3349. doi: 10.1038/s41467-021-23355-x.
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.
目前的免疫治疗模式旨在重振 CD8 T 细胞，但体液免疫对肿瘤免疫的贡献仍研究不足。在这里，我们证明在由人乳头瘤病毒感染（HPV）引起的头颈部鳞状细胞癌（HNSCC）中，患者具有生发中心（GC）肿瘤浸润 B 细胞（TIL-B）的转录特征和与三级淋巴结构（TLS）一致的免疫细胞空间组织，这两者都与良好的预后相关。HPV HNSCC 中的 GC TIL-B 具有与暗区、亮区和 GC B 细胞过渡状态一致的独特基因表达波。TLS 中 HPV HNSCC 的 GC TIL-B 上表达增强了 Sema4a，并且在 TIL-B 的分化过程中也表达增强。我们的研究表明，在未来的研究中应优先考虑增强 HNSCC 中 TIL-B 反应的治疗方法，以确定它们是否可以补充当前的 T 细胞介导的免疫疗法。
