Dendritic cells delivered inside human carcinomas are sequestered by interleukin-8.
In the course of a clinical trial consisting of intratumoral injections of dendritic cells (DCs) transfected to produce interleukin-12, the use of (111)In-labeled tracing doses of DCs showed that most DCs remained inside tumor tissue, instead of migrating out. In search for factors that could explain this retention, it was found that tumors from patients suffering hepatocellular carcinoma, colorectal or pancreatic cancer were producing IL-8 and that this chemokine attracted monocyte-derived dendritic cells that uniformly express both IL-8 receptors CXCR1 and CXCR2. Accordingly, neutralizing antihuman IL-8 monoclonal antibodies blocked the chemotactic attraction of DCs by recombinant IL-8, as well as by the serum of the patients or culture supernatants of human colorectal carcinomas. In addition, tissue culture supernatants of colon carcinoma cells inhibited DC migration induced by MIP-3beta in an IL-8-dependent fashion. IL-8 production in malignant tissue and the responsiveness of DCs to IL-8 are a likely explanation of the clinical images, which suggest retention of DCs inside human malignant lesions. Impairment of DC migration toward lymphoid tissue could be involved in cancer immune evasion.
Feijoó
Esperanza
E
Division of Hepatology and Gene Therapy, Clínica Universitaria/School of Medicine, Foundation for Applied Medical Research, Universidad de Navarra, Pamplona, Spain.
Alfaro
Carlos
C
Mazzolini
Guillermo
G
Serra
Patricia
P
Peñuelas
Iván
I
Arina
Ainhoa
A
Huarte
Eduardo
E
Tirapu
Iñigo
I
Palencia
Belén
B
Murillo
Oihana
O
Ruiz
Juan
J
Sangro
Bruno
B
Richter
José A
JA
Prieto
Jesús
J
Melero
Ignacio
I
D000911:Antibodies, Monoclonal; D002465:Cell Movement; D002633:Chemotaxis; D003110:Colonic Neoplasms / Q000276:immunology* / Q000628:therapy*; D003713:Dendritic Cells / Q000276:immunology*; D006801:Humans; D007167:Immunotherapy; D018664:Interleukin-12 / Q000096:biosynthesis; D016209:Interleukin-8 / Q000096:biosynthesis* / Q000276:immunology*; D008113:Liver Neoplasms / Q000276:immunology* / Q000628:therapy*; D010190:Pancreatic Neoplasms / Q000276:immunology* / Q000628:therapy*; D014162:Transfection
D000911:Antibodies, Monoclonal; D016209:Interleukin-8; D018664:Interleukin-12