SLC/CCL21-mediated anti-tumor responses require IFNgamma, MIG/CXCL9 and IP-10/CXCL10.
BACKGROUND
SLC/CCL21, normally expressed in high endothelial venules and in T cell zones of spleen and lymph nodes, strongly attracts T cells and dendritic cells (DC). We have previously shown that SLC/CCL21-mediated anti-tumor responses are accompanied by significant induction of IFNgamma and the CXC chemokines, monokine induced by IFNgamma (MIG/CXCL9) and IFNgamma-inducible protein-10 (IP-10/CXCL10).


RESULTS
We assessed the importance of IFNgamma, IP-10/CXCL10 and MIG/CXCL9 in SLC/CCL21 therapy. In vivo depletion of IP-10/CXCL10, MIG/CXCL9 or IFNgamma significantly reduced the anti-tumor efficacy of SLC/CCL21. Assessment of cytokine production at the tumor site showed an interdependence of IFNgamma, MIG/CXCL9 and IP-10/CXCL10; neutralization of any one of these cytokines caused a concomitant decrease in all three cytokines. Similarly, neutralization of any one of these cytokines led to a decrease in the frequency of CXCR3+ve T cells and CD11c+ve DC at the tumor site.


CONCLUSIONS
These findings indicate that the full potency of SLC/CCL21-mediated anti-tumor responses require in part the induction of IFNgamma, MIG/CXCL9 and IP-10/CXCL10.
Department of Medicine, UCLA Lung Cancer Research Program, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA. sharmasp@ucla.edu
Sherven
S
Sharma
Seok-Chul
SC
Yang
Sven
S
Hillinger
Li X
LX
Zhu
Min
M
Huang
Raj K
RK
Batra
Jeff F
JF
Lin
Marie D
MD
Burdick
Robert M
RM
Strieter
Steven M
SM
Dubinett
D000818:Animals; D018827:Carcinoma, Lewis Lung / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D054421:Chemokine CCL21; D054357:Chemokine CXCL10; D054370:Chemokine CXCL9; D019742:Chemokines, CC / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D019743:Chemokines, CXC / Q000276:immunology* / Q000378:metabolism; D007371:Interferon-gamma / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation
C515479:Ccl21c protein, mouse; D054421:Chemokine CCL21; D054357:Chemokine CXCL10; D054370:Chemokine CXCL9; D019742:Chemokines, CC; D019743:Chemokines, CXC; C485969:Cxcl9 protein, mouse; D007371:Interferon-gamma