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Enhancement of anti‐tumor immunity by tumor cells transfected with the secondary lymphoid tissue chemokine EBI‐1‐ligand chemokine and stromal cell–derived factor‐1αchemokine genes
Author(s) -
Nomura Tetsuhiko,
Hasegawa Hitoshi,
Kohno Masashi,
Sasaki Miho,
Fujita Shigeru
Publication year - 2001
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/1097-0215(200002)9999:9999<::aid-ijc1107>3.0.co;2-j
Subject(s) - chemokine , biology , stromal cell , cancer research , cxcl16 , immunology , lymph node stromal cell , cc chemokine receptors , chemokine receptor , immune system
Several new lymphocyte‐specific chemokines, which attract naive and memory T cells, B cells, dendritic cells and natural killer cells, have been isolated. We have found evidence of the anti‐tumor effects of 3 major lymphocyte‐specific chemokines, secondary lymphoid tissue chemokine (SLC), EBI‐1‐ligand chemokine (ELC) and stromal cell–derived factor (SDF)‐1α, in murine models (Meth A fibrosarcoma and HM‐1 ovarian tumor). In both naive and immunized mice, tumors expressing SLC, ELC or SDF‐1α showed delayed progression compared with control tumors. In mice immunized with tumor cells expressing 1 of these 3 chemokine genes, challenge with parental tumor cells resulted in slightly slower progression than in control mice, while in mice immunized with tumor cells transfected to co‐express IL‐2 or granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) as well as these chemokines, all tumors regressed. Furthermore, spleen cells from mice immunized with these “double‐transfected” tumor cells exhibited higher proliferative responses and greater cytotoxic activity against parental tumor cells. These anti‐tumor effects were associated with profound alterations in the leukocyte populations within the tumors and regional lymph nodes, and this was due to activation of type I T cell‐dependent responses that produced high levels of IFN‐γ. These findings show that SLC, ELC and SDF‐1α enhance anti‐tumor immunity both systemically and locally and that these chemokines may be clinically useful, especially when combined with IL‐2 and GM‐CSF. © 2001 Wiley‐Liss, Inc.