Induction of lymphoidlike stroma and immune escape by tumors that express the chemokine CCL21

Science. 2010 May 7;328(5979):749-52. doi: 10.1126/science.1185837. Epub 2010 Mar 25.


Tumor manipulation of host immunity is important for tumor survival and invasion. Many cancers secrete CCL21, a chemoattractant for various leukocytes and lymphoid tissue inducer cells, which drive lymphoid neogenesis. CCL21 expression by melanoma tumors in mice was associated with an immunotolerant microenvironment, which included the induction of lymphoid-like reticular stromal networks, an altered cytokine milieu, and the recruitment of regulatory leukocyte populations. In contrast, CCL21-deficient tumors induced antigen-specific immunity. CCL21-mediated immune tolerance was dependent on host rather than tumor expression of the CCL21 receptor, CCR7, and could protect distant, coimplanted CCL21-deficient tumors and even nonsyngeneic allografts from rejection. We suggest that by altering the tumor microenvironment, CCL21-secreting tumors shift the host immune response from immunogenic to tolerogenic, which facilitates tumor progression.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Antigen-Presenting Cells / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • Cell Line, Tumor
  • Chemokine CCL21 / metabolism*
  • Cytokines / metabolism
  • Disease Progression
  • Female
  • Immune Tolerance
  • Lymph Nodes / immunology
  • Lymphoid Tissue / immunology*
  • Lymphoid Tissue / pathology
  • Melanoma, Experimental / immunology*
  • Melanoma, Experimental / pathology*
  • Mice
  • Mice, Inbred C57BL
  • Neoplasm Transplantation
  • RNA Interference
  • Receptors, CCR7 / metabolism
  • Signal Transduction
  • Stromal Cells / immunology*
  • Stromal Cells / pathology
  • T-Lymphocytes / immunology
  • T-Lymphocytes, Regulatory / immunology
  • Tumor Escape*


  • Ccr7 protein, mouse
  • Chemokine CCL21
  • Cytokines
  • Receptors, CCR7