Tertiary Lymphoid Structures in Cancers: Prognostic Value, Regulation, and Manipulation for Therapeutic Intervention

Abstract

Tertiary lymphoid structures (TLS) are ectopic lymphoid aggregates that reflect lymphoid neogenesis occurring in tissues at sites of inflammation. They are detected in tumors where they orchestrate local and systemic anti-tumor responses. A correlation has been found between high densities of TLS and prolonged patient's survival in more than 10 different types of cancer. TLS can be regulated by the same set of chemokines and cytokines that orchestrate lymphoid organogenesis and by regulatory T cells. Thus, TLS offer a series of putative new targets that could be used to develop therapies aiming to increase the anti-tumor immune response.

Keywords: adaptive immune response; cancer; chemokine; tertiary lymphoid structure; tumor microenvironment.

Figure 1

Prognostic value of TLS-associated biomarkers in primary and metastatic cancers. The number of publications studying the impact of mature DCs, TLS-related gene signatures, B-cell aggregates, T cell aggregates, or H&E with regard to prognosis in human cancers is represented (12 cancer types have been included). Blue, orange, and red circles represent an association with good, none, and poor prognosis, respectively. The diameter of the circles represents the total number of tumors (n) that have been analyzed on these studies.