Li and Zhang et al. reported the presence of stem-like T cells and B cells at various stages of tertiary lymphoid structure (TLS) maturation in patient HNSCC tumors. Mature TLS (mTLS) were enriched for stem-like and functional CD8+ T cells, CD4+ Texprog/Tfh cells, and diverse subtypes of B cells and plasma cells. Immature TLS displayed an enrichment of B cells without concurrent plasma cells. Spatial transcriptomics confirmed the presence of triads of CD4+ Texprog/Tfh cells with DCs and B cells, suggesting mTLSs have a role in B cell maturation and effector memory CD8+ T cell generation. The presence of mTLSs was associated with response to ICB therapy in HNSCC.
Contributed by Shishir Pant
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 the germinal center, and interacting with DC-LAMP(+) dendritic cells to support CD8(+) T cell activation. Conversely, non-mTLS tumors do not promote local anti-tumor immunity which is abundant of immunosuppressive cells or a lack of stem-like B and T cells. Furthermore, patients with mTLS manifest improved overall survival and response to ICB compared to those with non-mTLS. Overall, our study provides insights into mechanisms underlying mTLS-mediated intra-tumoral immunity events against cancer.
Author Info: (1) State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, Sch
Author Info: (1) State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Frontier Science Center for Immunology and Metabolism, Taikang Center for Life and Medical Sciences, Wuhan University, Wuhan, China. Department of Oral Maxillofacial-Head Neck Oncology, School & Hospital of Stomatology, Wuhan University, Wuhan, China. (2) State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Frontier Science Center for Immunology and Metabolism, Taikang Center for Life and Medical Sciences, Wuhan University, Wuhan, China. (3) State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Frontier Science Center for Immunology and Metabolism, Taikang Center for Life and Medical Sciences, Wuhan University, Wuhan, China. (4) State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Frontier Science Center for Immunology and Metabolism, Taikang Center for Life and Medical Sciences, Wuhan University, Wuhan, China. (5) State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Frontier Science Center for Immunology and Metabolism, Taikang Center for Life and Medical Sciences, Wuhan University, Wuhan, China. (6) State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Frontier Science Center for Immunology and Metabolism, Taikang Center for Life and Medical Sciences, Wuhan University, Wuhan, China. (7) State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Frontier Science Center for Immunology and Metabolism, Taikang Center for Life and Medical Sciences, Wuhan University, Wuhan, China. (8) State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Frontier Science Center for Immunology and Metabolism, Taikang Center for Life and Medical Sciences, Wuhan University, Wuhan, China. (9) State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Frontier Science Center for Immunology and Metabolism, Taikang Center for Life and Medical Sciences, Wuhan University, Wuhan, China. (10) State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Frontier Science Center for Immunology and Metabolism, Taikang Center for Life and Medical Sciences, Wuhan University, Wuhan, China. (11) State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Frontier Science Center for Immunology and Metabolism, Taikang Center for Life and Medical Sciences, Wuhan University, Wuhan, China. dww@whu.edu.cn. Department of Oral Maxillofacial-Head Neck Oncology, School & Hospital of Stomatology, Wuhan University, Wuhan, China. dww@whu.edu.cn. (12) State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Frontier Science Center for Immunology and Metabolism, Taikang Center for Life and Medical Sciences, Wuhan University, Wuhan, China. sunzj@whu.edu.cn. Department of Oral Maxillofacial-Head Neck Oncology, School & Hospital of Stomatology, Wuhan University, Wuhan, China. sunzj@whu.edu.cn.
