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What licenses tumor niches is not fully understood: chemokines recruit cells but do not specify TLS-archetypal DC:CD4\u207aT:CD8\u207aT triad composition. We show that the organizing signal is a matrix fragment. Proteoglycan versican (VCAN) proteolysis releases the matrikine versikine constitutively in CXCL13-replete germinal center light zones. In tumors, versikine is released inducibly within CXCL13-rich stromal niches. Versikine activates CD11b\u207a cDC, expands cDC1, and suffices for triad assembly. Versikine-conditioned DC engage progenitor-exhausted CD8\u207a T-cells (Tpex) and Tpex-sustaining, Th1-polarized follicular helper CD4\u207a T-cells. Excess unproteolyzed VCAN inverts this toward DC\u2013Treg crosstalk and Tpex loss. Versikine (mRNA or recombinant protein) plus anti-PD-L1 eradicated experimental tumors reverse-translated to model adverse-prognosis, VCAN-proteolysis-weak patients from a prospective PD-1 blockade trial in oligometastatic colorectal cancer. The extracellular matrix instructs, rather than merely scaffolds, the multicellular units of antitumor immunity.<\/jats:p>","DOI":"10.64898\/2026.09.24.753585","type":"posted-content","created":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:11:07Z","timestamp":1790727067000},"source":"Crossref","is-referenced-by-count":0,"title":["A matrikine organizes the dendritic cell\u2013T cell triads that build tertiary lymphoid structures"],"prefix":"10.64898","author":[{"given":"Daniel J.","family":"Lagal","sequence":"first","affiliation":[{"name":"Rush University Medical Center, Chicago IL, USA"},{"name":"Rush MD Anderson Cancer Center, Chicago IL, USA"},{"name":"University of California San Diego, La Jolla CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Duncan","family":"Hong","sequence":"additional","affiliation":[{"name":"Rush University Medical Center, Chicago IL, USA"},{"name":"Rush MD Anderson Cancer Center, Chicago IL, USA"},{"name":"University of 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