title: Occurrence of tertiary lymphoid tissue is associated with T-cell infiltration and predicts better prognosis in early-stage colorectal cancers.
abstract: OBJECTIVE
  Tumor-infiltrating T lymphocytes (TIL) play a key role in the clinical outcome of human colorectal cancer; however, the dynamics of their recruitment along colorectal cancer clinical progression have not been fully elucidated. Tertiary lymphoid tissue (TLT) is an ectopic organized lymph node-like structure that typically forms at sites of chronic inflammation and is involved in adaptive immune responses. Its occurrence in cancer is sporadically documented and its role and clinical relevance is largely unknown.
  
  
  METHODS
  The occurrence of TLT, the correlation with TILs, and the clinical relevance were evaluated retrospectively, in a cohort study involving a consecutive series of 351 patients with stage II and III colorectal cancer. The role of TLT in lymphocyte recruitment was assessed in a preclinical model of colorectal cancer.
  
  
  RESULTS
  In both human colorectal cancer and in a murine model of colorectal cancer, we identified organized TLT, highly vascularized (including high endothelial venules), and correlated with the density of CD3(+) TILs. Intravenous injection in mice of GFP splenocytes resulted in homing of lymphocytes to TLT, suggesting an active role of TLT in the recruitment of lymphocytes to tumor areas. Accordingly, TLT density and TIL infiltration correlated and were coordinated in predicting better patient's outcome among patients with stage II colorectal cancer.
  
  
  CONCLUSIONS
  We provide evidence that TLT is associated with lymphocyte infiltration in colorectal cancer, providing a pathway of recruitment for TILs. TLT cooperates with TILs in a coordinated antitumor immune response, when identifying patients with low-risk early-stage colorectal cancer, thus, representing a novel prognostic biomarker for colorectal cancer.
authors: Authors' Affiliations: Departments of Immunology and Inflammation; and Gastroenterology; Laboratory of Molecular Gastroenterology, Humanitas Clinical and Research Center, Rozzano; and Department of Biotechnologies and Translational Medicine, University of Milan, Milan, Italy.
authors: Giuseppe
authors: G
authors: Di Caro
authors: Francesca
authors: F
authors: Bergomas
authors: Fabio
authors: F
authors: Grizzi
authors: Andrea
authors: A
authors: Doni
authors: Paolo
authors: P
authors: Bianchi
authors: Alberto
authors: A
authors: Malesci
authors: Luigi
authors: L
authors: Laghi
authors: Paola
authors: P
authors: Allavena
authors: Alberto
authors: A
authors: Mantovani
authors: Federica
authors: F
authors: Marchesi
mesh_terms: D000368:Aged; D000818:Animals; D017252:CD3 Complex / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D015179:Colorectal Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D018655:Lymphocyte Count; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology* / Q000378:metabolism; D008221:Lymphoid Tissue / Q000276:immunology* / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D011379:Prognosis; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D018570:Risk Assessment / Q000706:statistics & numerical data; D012307:Risk Factors; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
chemical_list: D017252:CD3 Complex