Colon carcinoma cells induce CXCL11-dependent migration of CXCR3-expressing cytotoxic T lymphocytes in organotypic culture.
Adoptive immunotherapy of cancer patients with cytolytic T lymphocytes (CTL) has been hampered by the inability of the CTL to home into tumors in vivo. Chemokines can attract T lymphocytes to the tumor site, as demonstrated in animal models, but the role of chemokines in T-lymphocyte trafficking toward human tumor cells is relatively unexplored. In the present study, the role of chemokines and their receptors in the migration of a colon carcinoma (CC) patient's CTL toward autologous tumor cells has been studied in a novel three-dimensional organotypic CC culture. CTL migration was mediated by chemokine receptor CXCR3 expressed by the CTL and CXCL11 chemokine secreted by the tumor cells. Excess CXCL11 or antibodies to CXCL11 or CXCR3 inhibited migration of CTL to tumor cells. T cell and tumor cell analyses for CXCR3 and CXCL11 expression, respectively, in ten additional CC samples, may suggest their involvement in other CC patients. Our studies, together with previous studies indicating angiostatic activity of CXCL11, suggest that CXCL11 may be useful as an immunotherapeutic agent for cancer patients when transduced into tumor cells or fused to tumor antigen-specific Ab.
Berencsi
Klara
K
The Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104, USA.
Meropol
Neal J
NJ
Hoffman
John P
JP
Sigurdson
Elin
E
Giles
Lydia
L
Rani
Pyapalli
P
Somasundaram
Rajasekharan
R
Zhang
Tianqian
T
Kalabis
Jiri
J
Caputo
Laura
L
Furth
Emma
E
Swoboda
Rolf
R
Marincola
Francesco
F
Herlyn
Dorothee
D
D017209:Apoptosis / Q000276:immunology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000276:immunology*; D054371:Chemokine CXCL11; D019743:Chemokines, CXC / Q000096:biosynthesis / Q000276:immunology*; D003110:Colonic Neoplasms / Q000276:immunology*; D016207:Cytokines / Q000032:analysis; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D010641:Phenotype; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine / Q000096:biosynthesis / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D046509:Tissue Culture Techniques
C515202:CXCL11 protein, human; C515187:CXCR3 protein, human; D054371:Chemokine CXCL11; D019743:Chemokines, CXC; D016207:Cytokines; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine