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Tertiary lymphoid structures (TLSs) are ectopic immune cell clusters formed in nonlymphoid tissues affected by persistent inflammation, such as in cancer and prolonged infections. They have features of the structure and function of secondary lymphoid organs, featuring central CD20+ B cells, surrounded by CD3+ T cells, CD21+ follicular dendritic cells, and CD68+ macrophages, with a complex vascular system. TLS formation is governed by lymphotoxin-α1β2, TNF, and chemokines like CCL19, CCL21, and CXCL13, differing from secondary lymphoid organ development in developing later in life at sites of chronic inflammation.
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