The Sunrise of Tertiary Lymphoid Structures in Cancer

First considered as a negative epiphenomenon in autoimmune and inflammatory diseases, with possible deleterious consequences through the production of pathological autoantibodies and antiself T cells, tertiary lymphoid structures (TLS) have gained major scientific and clinical interest in cancer due to their association with better clinical outcomes and improved responses to immunotherapy. Studies have investigated the structure and plasticity of TLS in the context of tumors and the role of the TLS B-cell compartment in contributing to the favorable clinical outcome of cancer patients. Identifying biomarkers that indicate the presence of TLS in tumors in a noninvasive manner could therefore represent a major advance in the diagnosis and treatment decision-making for these patients. Also, the interplay between TLS, tumor cells, and microbiota opens new avenues for deciphering the role of microorganisms in cancer development. Their use as TLS inducers further underlines the need for continued research in this field. Moreover, emerging data have emphasized the critical role of sensory and sympathetic nerves in regulating TLS formation and function. Finally, humanized mice may serve as valuable tools for developing preclinical models to study the role of human TLS in cancer, a much-needed goal. These different topics are discussed in the present review.