Se. Braun et al., The CC chemokine CK beta-11/MIP-3 beta/ELC/exodus 3 mediates tumor rejection of murine breast cancer cells through NK cells, J IMMUNOL, 164(8), 2000, pp. 4025-4031
CK beta-11 chemoattracts T cells, B cells, dendritic cells, macrophage prog
enitors, and NK cells and facilitates dendritic cell and T cell interaction
s in secondary lymphoid tissues. We hypothesized that expression of CK beta
-11 in tumor cells may generate antitumor immunity through these interactio
ns, After transduction with the retroviral vector L(CK beta 11)SN, the muri
ne breast cancer cell line C3L5 (C3L5-CK beta 11) showed expression of retr
oviral mRNA by Northern analysis and production of functional CK beta-11 by
chemotaxis of human NK cells to C3L5-CK beta 11 supernatant. Only 10% of m
ice injected with C3L5-CK beta 11 developed tumors, compared with 100% of m
ice injected with a transduced control C3L5 line (C3L5-G1N). Importantly, t
he in vitro growth characteristics of the CK beta-11-transduced cell line w
ere unaffected, suggesting the difference in growth in vivo was a result of
chemokine production, Vaccination with C3L5-CK beta 11 partially protected
animals from parental C3L5 challenge, Immunodepletion with anti-asialo-G(M
1) or anti-CD4 during C3L5-Cg beta 11 vaccination significantly reduced CK
beta-11 antitumor activity compared with control and anti-CD8-treated group
s. Splenocytes from NK-depleted animals transferred the acquired immunity g
enerated,vith C3L5-CK beta 11 vaccination, while splenocytes from the CD4-d
epleted animals did not, These results indicate, for the first time, that e
xpression of CK beta-11 in a breast cancer cell line mediates rejection of
the transduced tumor through a mechanism involving NK and CD4(+) cells. Fur
thermore, CK beta-11-transduced tumor cells generate long-term antitumor im
munity that re quires CD4(+) cells These studies demonstrate the potential
role of CK beta-11 as an adjuvant in stimulating antitumor responses.