Tertiary lymphoid structures as unique constructions associated with the organization, education, and function of tumor-infiltrating immunocytes.

Abstract

Tertiary lymphoid structures (TLSs) are formations at sites with persistent inflammatory stimulation, including tumors. These ectopic lymphoid organs mainly consist of chemo-attracting B cells, T cells, and supporting dendritic cells (DCs). Mature TLSs exhibit functional organization for the optimal development and collaboration of adaptive immune response, delivering an augmented effect on the tumor microenvironment (TME). The description of the positive correlation between TLSs and tumor prognosis is reliable only under a certain condition involving the localization and maturation of TLSs. Emerging evidence suggests that underlying mechanisms of the anti-tumor effect of TLSs pave the way for novel immunotherapies. Several approaches have been developed to take advantage of intratumoral TLSs, either by combining it with therapeutic agents or by inducing the neogenesis of TLSs.