title: High endothelial venules are rare in colorectal cancers but accumulate in extra-tumoral areas with disease progression.
abstract: Prolonged patient survival after surgical resection, is associated with a higher cytotoxic and memory T cell density within colorectal cancers (CRC). High endothelial venules (HEVs) are specialized blood vessels present in secondary lymphoid organs (SLO) that allow ingress of naïve and central memory T cells from the blood. It has been proposed that HEVs in tumors might serve as a similar route of entry for lymphocytes into the tumor and result in an improved prognosis. The present study aimed to characterize HEVs and their microenvironment in resected tumors from colorectal cancer patients (n= 62). We observed HEVs in association with lymphoid aggregates in 49 out of 62 patients. However, these HEV+lymphoid aggregates were largely at the invasive margin of the tumor and although there was an association with lymphocytes and HEVs at the invasive margin (p= 0.002) there was only a very weak association with tumor infiltrating lymphocytes. Indeed, lymphoid aggregates were associated with more advanced disease (Dukes' stage C) and did not indicate a favorable prognosis.
authors.affiliation: Infection and Immunity; School of Medicine; Henry Wellcome Building; Cardiff University ; Cardiff, UK.
authors.forename: Diana Costa
authors.initials: DC
authors.lastname: Bento
authors.affiliation: Infection and Immunity; School of Medicine; Henry Wellcome Building; Cardiff University ; Cardiff, UK.
authors.forename: Emma
authors.initials: E
authors.lastname: Jones
authors.affiliation: Infection and Immunity; School of Medicine; Henry Wellcome Building; Cardiff University ; Cardiff, UK.
authors.forename: Syed
authors.initials: S
authors.lastname: Junaid
authors.affiliation: Institute of Medical Genetics; University Hospital of Wales ; Cardiff, UK.
authors.forename: Justyna
authors.initials: J
authors.lastname: Tull
authors.affiliation: Institute of Cancer and Genetics; Cardiff University School of Medicine ; Cardiff, UK.
authors.forename: Geraint T
authors.initials: GT
authors.lastname: Williams
authors.affiliation: Infection and Immunity; School of Medicine; Henry Wellcome Building; Cardiff University ; Cardiff, UK.
authors.forename: Andrew
authors.initials: A
authors.lastname: Godkin
authors.affiliation: Infection and Immunity; School of Medicine; Henry Wellcome Building; Cardiff University ; Cardiff, UK.
authors.forename: Ann
authors.initials: A
authors.lastname: Ager
authors.affiliation: Infection and Immunity; School of Medicine; Henry Wellcome Building; Cardiff University ; Cardiff, UK.
authors.forename: Awen
authors.initials: A
authors.lastname: Gallimore
keywords: A/F, aggregate/ follicle; CRC, colorectal cancer; HEV, high endothelial venule; T cells; TILs, tumor-infiltrating lymphocytes; Treg, regulatory T cell.; colorectal cancer; high endothelial venules; lymphoid aggregates/follicles; tumor infiltrating lymphocytes and tertiary lymphoid organs