Limited amounts of dendritic cells migrate into the T-cell area of lymph nodes but have high immune activating potential in melanoma patients.
OBJECTIVE
The success of immunotherapy with dendritic cells (DC) to treat cancer is dependent on effective migration to the lymph nodes and subsequent activation of antigen-specific T cells. In this study, we investigated the fate of DC after intradermal (i.d.) or intranodal (i.n.) administration and the consequences for the immune activating potential of DC vaccines in melanoma patients.


METHODS
DC were i.d. or i.n. administered to 25 patients with metastatic melanoma scheduled for regional lymph node resection. To track DC in vivo with scintigraphic imaging and in lymph nodes by immunohistochemistry, cells were labeled with both [(111)In]-indium and superparamagnetic iron oxide.


RESULTS
After i.d. injection, maximally 4% of the DC reached the draining lymph nodes. When correctly delivered, all DC were delivered to one or more lymph nodes after i.n. injection. Independent of the route of administration, large numbers of DC remained at the injection site, lost viability, and were cleared by infiltrating CD163+ macrophages within 48 hours. Interestingly, 87 +/- 10% of the surviving DC preferentially migrated into the T-cell areas, where they induced antigen-specific T-cell responses. Even though more DC reached the T-cell areas, i.n. injection of DC induced similar antigen-specific immune responses as i.d. injection. Immune responses were already induced with <5 x 10(5) DC migrating into the T-cell areas.


CONCLUSIONS
Monocyte-derived DC have high immune activating potential irrespective of the route of vaccination. Limited numbers of DC in the draining lymph nodes are sufficient to induce antigen-specific immunologic responses.
Verdijk
Pauline
P
Department of Tumor Immunology, Nijmegen Centre for Molecular Life Science, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
Aarntzen
Erik H J G
EH
Lesterhuis
W Joost
WJ
Boullart
A C Inge
AC
Kok
Ellemieke
E
van Rossum
Michelle M
MM
Strijk
Simon
S
Eijckeler
Femke
F
Bonenkamp
Johannes J
JJ
Jacobs
Joannes F M
JF
Blokx
Willeke
W
Vankrieken
J Han J M
JH
Joosten
Irma
I
Boerman
Otto C
OC
Oyen
Wim J G
WJ
Adema
Gosse
G
Punt
Cornelis J A
CJ
Figdor
Carl G
CG
de Vries
I Jolanda M
IJ