Priming of naive T cells inside tumors leads to eradication of established tumors.
The tumor barrier comprised of nonantigenic stromal cells may contribute to the failure of tumor rejection. The tumor-necrosis factor superfamily member LIGHT (also known as TNFSF-14) is a ligand of stromal cell-expressed lymphotoxin-beta receptor and T cell-expressed herpes viral entry mediator (HVEM). Here we show that forced expression of LIGHT in the tumor environment induces a massive infiltration of naive T lymphocytes that correlates with an upregulation of both chemokine production and expression of adhesion molecules. Activation of these infiltrating T cells, possibly through HVEM, leads to the rejection of established, highly progressive tumors at local and distal sites. Our study indicates that targeting the tumor barrier may be an effective strategy for cancer immunotherapy.
Yu
Ping
P
The Committee on Immunology and Department of Pathology, University of Chicago, MC3083, Chicago, IL 60637, USA.
Lee
Youjin
Y
Liu
Wenhua
W
Chin
Robert K
RK
Wang
Jing
J
Wang
Yang
Y
Schietinger
Andrea
A
Philip
Mary
M
Schreiber
Hans
H
Fu
Yang-Xin
YX
D000818:Animals; D015815:Cell Adhesion Molecules / Q000096:biosynthesis; D018925:Chemokines / Q000096:biosynthesis; D005260:Female; D015870:Gene Expression; D006084:Graft Rejection; D007167:Immunotherapy / Q000379:methods*; D008213:Lymphocyte Activation; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D018448:Models, Immunological; D009368:Neoplasm Transplantation; D018124:Receptors, Tumor Necrosis Factor / Q000276:immunology; D053240:Receptors, Tumor Necrosis Factor, Member 14; D011991:Receptors, Virus / Q000276:immunology; D012513:Sarcoma, Experimental / Q000276:immunology* / Q000628:therapy*; D013601:T-Lymphocytes / Q000276:immunology*; D014161:Transduction, Genetic; D053326:Tumor Necrosis Factor Ligand Superfamily Member 14; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology*; D014611:Vaccination
D015815:Cell Adhesion Molecules; D018925:Chemokines; D008565:Membrane Proteins; D018124:Receptors, Tumor Necrosis Factor; D053240:Receptors, Tumor Necrosis Factor, Member 14; D011991:Receptors, Virus; C506029:Tnfrsf14 protein, mouse; C505915:Tnfsf14 protein, mouse; D053326:Tumor Necrosis Factor Ligand Superfamily Member 14; D014409:Tumor Necrosis Factor-alpha