Intravenous administration of MIP-1alpha with intra-tumor injection of P. acnes shows potent anti-tumor effect.
Dendritic cells (DCs) play a key role as potent biological adjuvants in anti-tumor host responses. However, DC-based vaccination does not always eradicate tumors effectively. Clinical evidence suggests that a strategy to recruit a substantial number of DCs into the tumor mass might provoke proficient anti-tumor immune responses. Here we describe that myeloid DCs (mDCs) efficiently accumulate in tumor sites after intravenous injection of recombinant macrophage inflammatory protein (MIP)-1alpha when pretreated locally with adjuvants like Propionibacterium acnes. Combined treatment of tumor-bearing mice with MIP-1alpha and P. acnes also recruited a large number of natural killer cells (NK cells) to both tumor sites and regional lymph nodes (LNs) and induced a strong T helper 1 immunity at an early time. This early response later led to accumulation of CD8(+) T cells, retraction of tumors and survival of animals treated with P. acnes/MIP-1alpha. In vivo depletion of NK cells or CD8(+) T cells impaired anti-tumor effects, suggesting that activation of NK cells and CD8(+) T cells contributes to anti-tumor immunity in this model. Therefore, this study provides a novel therapeutic strategy for cancer treatment using MIP-1alpha and certain adjuvants.
Nakano
Akiko
A
Department of Molecular Preventive Medicine & SORST, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Yoneyama
Hiroyuki
H
Ueha
Satoshi
S
Kitabatake
Masahiro
M
Ishikawa
Sho
S
Kawase
Ichiro
I
Sugiyama
Haruo
H
Matsushima
Kouji
K
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D018827:Carcinoma, Lewis Lung / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D003131:Combined Modality Therapy; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology; D005260:Female; D007275:Injections, Intravenous; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology; D019402:Macrophage Inflammatory Proteins / Q000008:administration & dosage*; D051379:Mice; D008810:Mice, Inbred C57BL; D011425:Propionibacterium acnes; D047368:Tumor Burden / Q000187:drug effects
D000970:Antineoplastic Agents; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D019402:Macrophage Inflammatory Proteins