Intravenous administration of MIP-1alpha with intra-tumor injection of P. acnes shows potent anti-tumor effect

Int Immunopharmacol. 2007 Jun;7(6):845-57. doi: 10.1016/j.intimp.2007.02.005. Epub 2007 Mar 9.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage*
  • CD8-Positive T-Lymphocytes / drug effects
  • CD8-Positive T-Lymphocytes / immunology
  • Carcinoma, Lewis Lung / immunology
  • Carcinoma, Lewis Lung / pathology
  • Carcinoma, Lewis Lung / therapy*
  • Cell Line
  • Cell Movement / drug effects
  • Chemokine CCL3
  • Chemokine CCL4
  • Combined Modality Therapy
  • Dendritic Cells / drug effects*
  • Dendritic Cells / immunology
  • Female
  • Injections, Intravenous
  • Killer Cells, Natural / drug effects
  • Killer Cells, Natural / immunology
  • Lymph Nodes / immunology
  • Macrophage Inflammatory Proteins / administration & dosage*
  • Mice
  • Mice, Inbred C57BL
  • Propionibacterium acnes*
  • Tumor Burden / drug effects

Substances

  • Antineoplastic Agents
  • Chemokine CCL3
  • Chemokine CCL4
  • Macrophage Inflammatory Proteins