Tumor-Associated Tertiary Lymphoid Structures: A Cancer Biomarker and a Target for Next-generation Immunotherapy

The different forms of lymphoid organization that coexist in our bodies appeared at distinct time points during the evolution of the animal kingdom. Some of these forms are constitutive, either in fully dedicated organs, such as lymph nodes, or in tissue interfacing with the external environment, such as mucosal-associated lymphoid tissues. Others, known as tertiary lymphoid structures (TLS), are selectively induced in response to inflammation in any peripheral tissues and organs. In this chapter, we discuss the functional interest of each of these lymphoid organizations under different physiopathological conditions. In the context of cancer, recent findings have identified TLS formation as a hallmark of active T- and B-cell immune responses against tumors. TLS are thus a powerful prognostic factor in nearly all solid cancers, which must be taken into account along with the tumor microenvironment. The presence of TLS also predicts the response to immunotherapy including immune checkpoint blockade. With tumor-associated TLS now a key target for the next generation of immunotherapy, this chapter discusses their potential therapeutic manipulations in oncology.