LTβR Agonist and IFN-I Cooperatively Induce Antitumor Tertiary Lymphoid Structure Formation: Mechanisms and Therapeutic Prospects
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Keywords
tertiary lymphoid structures, LTβR agonist, type I interferon, tumor immunotherapy
Abstract
This review systematically explores the antitumor strategy of combining lymphoxin beta receptor agonists with type I interferons to induce tertiary lymphoid structure formation, thereby transforming “cold” tumors into “hot” tumors. The article pointed out that this combination therapy can synergistically overcome the microenvironmental barriers of “cold” tumors: LTβR agonists provide structural scaffolds for the formation of tertiary lymphoid structures by activating tumor stromal cells, especially inducing high endothelial vein generation to promote lymphocyte homing; Type I interferon, on the other hand, provides powerful immune activation signals through its downstream signaling pathway, including promoting the recruitment and activation of B cells and T cells, enhancing the function of antigen-presenting cells, and driving B cells to differentiate into follicular-like B cells. Preclinical studies have confirmed that this strategy can effectively enhance the efficacy of existing therapies such as immune checkpoint inhibitors and chimeric antigen receptor T cells, and induce durable anti-tumor immune memory in neoadjuvant therapy, showing broad clinical translation prospects.
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