title: Tumoral lymphocytic infiltration and expression of the chemokine CXCL10 in breast cancers from the Ontario Familial Breast Cancer Registry.
abstract: OBJECTIVE
  Breast carcinomas, including basal and hereditary cases, often present with a prominent tumoral lymphocytic infiltrate. Chemokines could play a role in attracting these cells and contribute to tumor progression. We explored tumoral expression of CXCL10 and determined the relationship between CXCL10 and lymphocytic infiltrate in a cohort of breast cancers.
  
  
  METHODS
  Using tissue microarrays of 364 breast tumors, we evaluated expression of CXCL10 and its receptor, CXCR3, in relation to histopathologic features, biomarkers, and lymphocyte markers. In addition, we overexpressed CXCL10 and CXCR3 in MCF7 breast cancer cells and monitored T-lymphocyte migration and invasion.
  
  
  RESULTS
  Forty-five percent of tumors expressed CXCL10, and a significant association was found with CXCR3 and lymphocytic infiltrate. Further characterization of the lymphocytic infiltrate revealed an association with CXCL10 expression for peritumoral CD4+ and CD8+ lymphocytes. CD8+ intratumoral lymphocytes, FOXP3+ regulatory T cells (Tregs), and T-BET+ T(H)1 cells were associated with BRCA1 and basal tumors. Conditioned media from MCF7 cells overexpressing both CXCL10 and CXCR3 increased T-lymphocyte migration and invasion.
  
  
  CONCLUSIONS
  Our findings suggest that CXCL10 may act in a paracrine manner, affecting the tumor microenvironment, and in an autocrine manner, acting on the tumor cells themselves and may play a role in tumor invasiveness and progression. The CXCL10-CXCR3 axis can serve as a potential target in BRCA1 and basal breast cancers, which present with a prominent lymphocytic infiltrate and a poor prognosis. Clin Cancer Res; 19(2); 336-46. ©2012 AACR.
authors.affiliation: Keenan Research Centre, Li Ka Shing Knowledge Institute of St. Michael's Hospital, University of Toronto, Ontario, Canada.
authors.forename: Anna Marie
authors.initials: AM
authors.lastname: Mulligan
authors.forename: Irene
authors.initials: I
authors.lastname: Raitman
authors.forename: Linda
authors.initials: L
authors.lastname: Feeley
authors.forename: Dushanthi
authors.initials: D
authors.lastname: Pinnaduwage
authors.forename: Linh T
authors.initials: LT
authors.lastname: Nguyen
authors.forename: Frances P
authors.initials: FP
authors.lastname: O'Malley
authors.forename: Pamela S
authors.initials: PS
authors.lastname: Ohashi
authors.forename: Irene L
authors.initials: IL
authors.lastname: Andrulis
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D001943:Breast Neoplasms / Q000235:genetics* / Q000276:immunology* / Q000401:mortality / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000276:immunology; D054357:Chemokine CXCL10 / Q000235:genetics*; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D008214:Lymphocytes / Q000276:immunology / Q000378:metabolism; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D009864:Ontario; D054367:Receptors, CXCR3 / Q000235:genetics / Q000378:metabolism; D012042:Registries; D020825:T-Box Domain Proteins / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D000098815:T-bet Transcription Factor
chemical_list: D015415:Biomarkers; D054357:Chemokine CXCL10; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D054367:Receptors, CXCR3; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor