title: Tumor rejection and immune memory elicited by locally released LEC chemokine are associated with an impressive recruitment of APCs, lymphocytes, and granulocytes.
abstract: The human beta chemokine known as LEC (also called NCC-4, HCC-4, or LMC) displays chemotactic activity for monocytes and dendritic cells. The possibility that its local presence increases tumor immunogenicity is addressed in this paper. TSA parental cells (TSA-pc) are poorly immunogenic adenocarcinoma cells that grow progressively, kill both nu/nu and syngeneic BALB/c mice, and give rise to lung metastases. TSA cells engineered to release LEC (TSA-LEC) are still able to grow in nu/nu mice, but are promptly rejected and display a marginal metastatic phenotype in BALB/c mice. Rejection is associated with a marked T lymphocyte and granulocyte infiltration, along with extensive macrophage and dendritic cell recruitment. NK cells and CD4+ T lymphocytes are uninfluential in TSA-LEC cell rejection, whereas both CD8+ lymphocytes and polymorphonuclear leukocytes play a major role. An antitumor immune memory is established very quickly after rejection, since 6 days later 75% of BALB/c mice were already resistant to a TSA-pc challenge. Spleen cells from rejecting mice display specific cytotoxic activity against TSA-pc and secrete IFN-gamma and IL-2 when restimulated by TSA-pc. The ability of LEC to markedly improve recognition of poorly immunogenic cells by promoting APC-T cell cross-talk suggests that it could be an effective component of antitumor vaccines.
authors.affiliation: Department of Clinical and Biological Sciences, University of Torino, Orbassano, Italy. mirella.giovarelli@unito.it
authors.forename: M
authors.initials: M
authors.lastname: Giovarelli
authors.forename: P
authors.initials: P
authors.lastname: Cappello
authors.forename: G
authors.initials: G
authors.lastname: Forni
authors.forename: T
authors.initials: T
authors.lastname: Salcedo
authors.forename: P A
authors.initials: PA
authors.lastname: Moore
authors.forename: D W
authors.initials: DW
authors.lastname: LeFleur
authors.forename: B
authors.initials: B
authors.lastname: Nardelli
authors.forename: E
authors.initials: E
authors.lastname: Di Carlo
authors.forename: P L
authors.initials: PL
authors.lastname: Lollini
authors.forename: S
authors.initials: S
authors.lastname: Ruben
authors.forename: S
authors.initials: S
authors.lastname: Ullrich
authors.forename: G
authors.initials: G
authors.lastname: Garotta
authors.forename: P
authors.initials: P
authors.lastname: Musiani
mesh_terms: D000230:Adenocarcinoma / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000473:pathology*; D002455:Cell Division / Q000276:immunology; D002465:Cell Movement / Q000276:immunology*; D019742:Chemokines, CC / Q000378:metabolism / Q000502:physiology*; D005260:Female; D006084:Graft Rejection / Q000276:immunology* / Q000473:pathology; D006087:Graft vs Host Reaction / Q000276:immunology; D006098:Granulocytes / Q000276:immunology / Q000473:pathology*; D006801:Humans; D007156:Immunologic Memory; D008214:Lymphocytes / Q000276:immunology / Q000473:pathology*; D008325:Mammary Neoplasms, Experimental / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D014407:Tumor Cells, Cultured
chemical_list: C481939:CCL16 protein, human; D019742:Chemokines, CC