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 language | English |
|---|---|
| Pages (from-to) | 749-752 |
| Number of pages | 4 |
| Journal | Science |
| Volume | 328 |
| Issue number | 5979 |
| DOIs | |
| State | Published - May 7 2010 |
| Externally published | Yes |
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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 journal › Article
}
TY - JOUR
T1 - Induction of lymphoidlike stroma and immune escape by tumors that express the chemokine CCL21
AU - Shields, Jacqueline D.
AU - Kourtis, Iraklis C.
AU - Tomei, Alice
AU - Roberts, Joanna M.
AU - Swartz, Melody A.
PY - 2010/5/7
Y1 - 2010/5/7
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=77952231121&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77952231121&partnerID=8YFLogxK
U2 - 10.1126/science.1185837
DO - 10.1126/science.1185837
M3 - Article
C2 - 20339029
AN - SCOPUS:77952231121
VL - 328
SP - 749
EP - 752
JO - Science
JF - Science
SN - 0036-8075
IS - 5979
ER -