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

Jacqueline D. Shields, Iraklis C. Kourtis, Alice Tomei, Joanna M. Roberts, Melody A. Swartz

Research output: Contribution to journalArticle

276 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)749-752
Number of pages4
JournalScience
Volume328
Issue number5979
DOIs
StatePublished - May 7 2010
Externally publishedYes

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Chemokine CCL21
Tumor Escape
Neoplasms
Immunity
CCR7 Receptors
Leukocytes
Immune Tolerance
Tumor Microenvironment
Chemotactic Factors
Lymphoid Tissue
Neoplasm Antigens
Helper-Inducer T-Lymphocytes
Allografts
Melanoma
Cytokines

ASJC Scopus subject areas

  • General

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Induction of lymphoidlike stroma and immune escape by tumors that express the chemokine CCL21. / Shields, Jacqueline D.; Kourtis, Iraklis C.; Tomei, Alice; Roberts, Joanna M.; Swartz, Melody A.

In: Science, Vol. 328, No. 5979, 07.05.2010, p. 749-752.

Research output: Contribution to journalArticle

Shields, Jacqueline D. ; Kourtis, Iraklis C. ; Tomei, Alice ; Roberts, Joanna M. ; Swartz, Melody A. / Induction of lymphoidlike stroma and immune escape by tumors that express the chemokine CCL21. In: Science. 2010 ; Vol. 328, No. 5979. pp. 749-752.
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