Fig. 2

The roles of TLS in tumour immunity. (a) Anti-tumour effects of immune cell crosstalk in TLS. In the germinal centre (GC) of TLS, GC B cells differentiate into memory B cells and plasma cells (PCs) after receiving antigen delivery from FDCs and interacting with T follicular helper cells (Tfh). In the T-cell compartment, differentiated B cells and dendritic cells (DCs) present antigenic peptides to effector T cells, promoting infiltration of effector T cells into the tumour bed. Plasma cells follow the trajectory of fibroblasts into the tumour bed and produce anti-tumour IgG antibodies. In tumours, memory B cells can destroy tumour cells by expressing tumour necrosis factor-associated apoptosis-inducing ligand (TRAIL) or releasing granzyme B. Fc receptors on natural killer (NK) cells and macrophages can bind to a constant region of anti-tumour antibodies and destroy tumour cells through antibody-dependent cell-mediated cytotoxicity (ADCC) or antibody-dependent cell-mediated phagocytosis (ADCP). (b) Tumour-promoting effect of immune cell crosstalk in TLS. IgA PCs are associated with the secretion of suppressor cytokines, which generate an immunosuppressive environment favouring the emergence of M2 macrophages, myeloid-derived suppressor cells (MDSC), regulatory T (Treg) cells, and B (Breg) cells, and suppressing the function of effector T cells. Th2 cells produce IL-4 and IL-13, respectively, which promote tumour entry into the circulation by increasing epidermal growth factor expression and indirectly inhibit effector T cell function by increasing TGF-β production by MDSC. Macrophages upregulate PD-L1 to support local immunosuppression after ADCP. Complement component 1q (C1q) produced by macrophages binds to IgG-covered tumour cells, activating the classical complement cascade reaction and promoting tumour growth and angiogenesis. B Cells also produce VEGF, which promotes angiogenesis