Tumor rejection and immune memory elicited by locally released LEC chemokine are associated with an impressive recruitment of APCs, lymphocytes, and granulocytes.
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.
Giovarelli
M
M
Department of Clinical and Biological Sciences, University of Torino, Orbassano, Italy. mirella.giovarelli@unito.it
Cappello
P
P
Forni
G
G
Salcedo
T
T
Moore
P A
PA
LeFleur
D W
DW
Nardelli
B
B
Di Carlo
E
E
Lollini
P L
PL
Ruben
S
S
Ullrich
S
S
Garotta
G
G
Musiani
P
P
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
C481939:CCL16 protein, human; D019742:Chemokines, CC