Mature tertiary lymphoid structures evoke intra-tumoral T and B cell responses via progenitor exhausted CD4+ T cells in head and neck cancer

Abstract Tumor tertiary lymphoid structures (TLS), especially mature TLS (mTLS), have been associated with better prognosis and improved responses to immune checkpoint blockade (ICB), but the underlying mechanisms remain incompletely understood. Here, by performing single-cell RNA, antigen receptor sequencing and spatial transcriptomics on tumor tissue from head and neck squamous cell carcinoma (HNSCC) patients with different statuses of TLS, we observe that mTLS are enriched with stem-like T cells, and B cells at various maturation stages. Notably, progenitor exhausted CD4 + T cells, with features resembling follicular helper T cells, support these responses, by activating B cells to produce plasma cells in…

• NN
  National Natural Science Foundation of China

  Awards: 82303328, 82472818, 2042022dx0003, 82273202, 82103336, 2022YFC2504200
• WU
  Wuhan University

  Award: XNJC202303
• NK
  National Key Research and Development Program of China

  Award: 2022YFC2504200
• FR
  Fundamental Research Funds for the Central Universities

  Awards: 2042023kf0141, 2042024kf0021, 2042022dx0003