PMID- 10706711 OWN - NLM STAT- MEDLINE DCOM- 20000328 LR - 20190515 IS - 0022-1767 (Print) IS - 0022-1767 (Linking) VI - 164 IP - 6 DP - 2000 Mar 15 TI - Tumor rejection and immune memory elicited by locally released LEC chemokine are associated with an impressive recruitment of APCs, lymphocytes, and granulocytes. PG - 3200-6 AB - 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. FAU - Giovarelli, M AU - Giovarelli M AD - Department of Clinical and Biological Sciences, University of Torino, Orbassano, Italy. mirella.giovarelli@unito.it FAU - Cappello, P AU - Cappello P FAU - Forni, G AU - Forni G FAU - Salcedo, T AU - Salcedo T FAU - Moore, P A AU - Moore PA FAU - LeFleur, D W AU - LeFleur DW FAU - Nardelli, B AU - Nardelli B FAU - Di Carlo, E AU - Di Carlo E FAU - Lollini, P L AU - Lollini PL FAU - Ruben, S AU - Ruben S FAU - Ullrich, S AU - Ullrich S FAU - Garotta, G AU - Garotta G FAU - Musiani, P AU - Musiani P LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Immunol JT - Journal of immunology (Baltimore, Md. : 1950) JID - 2985117R RN - 0 (CCL16 protein, human) RN - 0 (Chemokines, CC) SB - IM MH - Adenocarcinoma/immunology/metabolism/pathology MH - Animals MH - Antigen-Presenting Cells/immunology/*pathology MH - Cell Division/immunology MH - Cell Movement/*immunology MH - Chemokines, CC/metabolism/*physiology MH - Female MH - Graft Rejection/*immunology/pathology MH - Graft vs Host Reaction/immunology MH - Granulocytes/immunology/*pathology MH - Humans MH - *Immunologic Memory MH - Lymphocytes/immunology/*pathology MH - Mammary Neoplasms, Experimental/*immunology/metabolism/pathology MH - Mice MH - Mice, Inbred BALB C MH - Mice, Nude MH - Tumor Cells, Cultured EDAT- 2000/03/08 09:00 MHDA- 2000/04/01 09:00 CRDT- 2000/03/08 09:00 PHST- 2000/03/08 09:00 [pubmed] PHST- 2000/04/01 09:00 [medline] PHST- 2000/03/08 09:00 [entrez] AID - ji_v164n6p3200 [pii] AID - 10.4049/jimmunol.164.6.3200 [doi] PST - ppublish SO - J Immunol. 2000 Mar 15;164(6):3200-6. doi: 10.4049/jimmunol.164.6.3200.