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 β 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-γ 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.

Vaccination With ENO1 DNA Prolongs Survival of Genetically Engineered Mice With Pancreatic Cancer

“…The antibody titer is expressed as serum binding potential ϫ 10 Ϫ3 /mL, calculated as previously described in detail. 11 Complement-dependent cytotoxicity. DT6606 or K8484 cells were seeded in a 96-well plate (5 ϫ 10 3 /well) in Dulbecco's modified Eagle medium/1% fetal bovine serum overnight for adhesion.…”

Enhanced expression of Duffy antigen receptor for chemokines by breast cancer cells attenuates growth and metastasis potential

“…Interleukin-13 receptor (IL-13R) overexpression profoundly inhibited MDA-MB-231 tumor in athymic nude mice, but no difference in vitro growth was found between the transfected cells and mock cells (Kawakami et al, 2001). These phenomenon also exist for many chemokines, such as CCL16 (liverexpressed chemokine, LEC) (Giovarelli et al, 2000) and CCL19 (EBI1-ligand chemokine, ELC) (Braun et al, 2000).…”

Liver-Expressed Chemokine/CC Chemokine Ligand 16 Attracts Eosinophils by Interacting with Histamine H4 Receptor

“…CCL16 was shown to be induced in monocytes by IL-10 (3) and chemotactic for monocytes and lymphocytes (3,4). In addition, this chemokine was shown to have a potent myelosuppressive activity comparable to that of MIP-1␣/CCL3 (4) and to induce tumor rejection (7). Previously, we have shown that CCL16 is a low-affinity functional ligand for CCR1, CCR2, and CCR5 (6).…”

“…To examine whether any chemokines act as an agonist for the histamine receptors, we performed calcium mobilization assays using murine L1.2 pre-B cells stably expressing H1, H2, or H4 (L1.2-H1, L1.2-H2, and L1.2-H4, respectively). Among 32 recombinant human chemokines tested at 100 nM (CC chemokines: CCL1, 2, 3, 4,5,7,8,11,13,14,15,16,17,18,19,20,21,22,24,25,26,27, and 28; CXC chemokines: CXCL4, 8, 9, 10, 12, 13, and 16; XCL1; CX3CL1), CCL16 was found to induce vigorous calcium mobilization in L1.2-H4. Fig.…”