The CC chemokine CKβ-11/MIP-3β/ELC/exodus 3 mediates tumor rejection of murine breast cancer cells through NK cells

Stephen E. Braun, Keyue Chen, Richard G. Foster, Chang H. Kim, Robert Hromas, Mark H. Kaplan, Hal E. Broxmeyer, Kenneth Cornetta

Research output: Contribution to journalArticlepeer-review

113 Scopus citations

Abstract

CKβ-11 chemoattracts T cells, B cells, dendritic cells, macrophage progenitors, and NK cells and facilitates dendritic cell and T cell interactions in secondary lymphoid tissues. We hypothesized that expression of CKβ-11 in tumor cells may generate antitumor immunity through these interactions. After transduction with the retroviral vector L(CKβ11)SN, the murine breast cancer cell line C3L5 (C3L5-CKβ11) showed expression of retroviral mRNA by Northern analysis and production of functional CKβ-11 by chemotaxis of human NK cells to C3L5-CKβ11 supernatant. Only 10% of mice injected with C3L5-CKβ11 developed tumors, compared with 100% of mice injected with a transduced control C3L5 line (C3L5-G1N). Importantly, the in vitro growth characteristics' of the CKβ-11-transduced cell line were unaffected, suggesting the difference in growth in vivo was a result of chemokine production. Vaccination with C3L5-CKβ11 partially protected animals from parental C3L5 challenge. Immunodepletion with anti-asialo-G(M1) or anti-CD4 during C3L5-CKβ11 vaccination significantly reduced CKβ-11 antitumor activity compared with control and anti-CD8-treated groups. Splenocytes from NK-depleted animals transferred the acquired immunity generated with C3L5-CKβ11 vaccination, while splenocytes from the CD4- depleted animals did not. These results indicate, for the first time, that expression of CKβ-11 in a breast cancer cell line mediates rejection of the transduced tumor through a mechanism involving NK and CD4+ cells. Furthermore, CKβ-11-transduced tumor cells generate long-term antitumor immunity that requires CD4+ cells. These studies demonstrate the potential role of CKβ-11 as an adjuvant in stimulating antitumor responses.

Original languageEnglish (US)
Pages (from-to)4025-4031
Number of pages7
JournalJournal of Immunology
Volume164
Issue number8
DOIs
StatePublished - Apr 15 2000

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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