TY - JOUR
T1 - Limited amounts of dendritic cells migrate into the T-cell area of lymph nodes but have high immune activating potential in melanoma patients
AU - Verdijk, Pauline
AU - Aarntzen, Erik H J G
AU - Lesterhuis, W Joost
AU - Boullart, A C Inge
AU - Kok, Ellemieke
AU - van Rossum, Michelle M
AU - Strijk, Simon
AU - Eijckeler, Femke
AU - Bonenkamp, Johannes J
AU - Jacobs, Joannes F M
AU - Blokx, Willeke
AU - Vankrieken, J Han J M
AU - Joosten, Irma
AU - Boerman, Otto C
AU - Oyen, Wim J G
AU - Adema, Gosse
AU - Punt, Cornelis J A
AU - Figdor, Carl G
AU - de Vries, I Jolanda M
PY - 2009/4/1
Y1 - 2009/4/1
N2 - PURPOSE: 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.EXPERIMENTAL DESIGN: 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.
AB - PURPOSE: 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.EXPERIMENTAL DESIGN: 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.
KW - Cancer Vaccines/administration & dosage
KW - Cell Movement
KW - Dendritic Cells/immunology
KW - Humans
KW - Injections
KW - Lymph Nodes/immunology
KW - Lymphocyte Activation
KW - Melanoma/immunology
KW - Phagocytosis
KW - Skin Neoplasms/immunology
KW - T-Lymphocytes/immunology
U2 - 10.1158/1078-0432.CCR-08-2729
DO - 10.1158/1078-0432.CCR-08-2729
M3 - Article
C2 - 19318472
SN - 1078-0432
VL - 15
SP - 2531
EP - 2540
JO - Clinical cancer research : an official journal of the American Association for Cancer Research
JF - Clinical cancer research : an official journal of the American Association for Cancer Research
IS - 7
ER -