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Updated: May 9, 2026
Cell Lineage Analyses and Gene Function Studies Using Twin-spot MARCM
Published on: March 2, 2017
Examination of MARCO activity on dendritic cell phenotype and function using a gene knockout mouse
Hiroshi Komine1, Lisa Kuhn, Norimasa Matsushita
1Immunology Program, H Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, United States of America.
Abstract:
We have reported the upregulation of MARCO, a member of the class A scavenger receptor family, on the surface of murine and human dendritic cells (DCs) pulsed with tumor lysates. Exposure of murine tumor lysate-pulsed DCs to an anti-MARCO antibody led to loss of dendritic-like processes and enhanced migratory capacity. In this study, we have further examined the biological and therapeutic implications of MARCO expression by DCs. DCs generated from the bone marrow (bm) of MARCO knockout (MARCO⁻/⁻) mice were phenotypically similar to DCs generated from the bm of wild-type mice and produced normal levels of IL-12 and TNF-α when exposed to LPS. MARCO⁻/⁻ DCs demonstrated enhanced migratory capacity in response to CCL-21 in vitro. After subcutaneous injection into mice, MARCO⁻/⁻ TP-DCs migrated more efficiently to the draining lymph node leading to enhanced generation of tumor-specific IFN-γ producing T cells and improved tumor regression and survival in B16 melanoma-bearing mice. These results support targeting MARCO on the surface of DCs to improve trafficking and induction of anti-tumor immunity.
Insights
Targeting MARCO on dendritic cells (DCs) enhances their migration and anti-tumor immunity. Blocking MARCO improves T cell response, leading to better tumor regression and survival in melanoma models.
Area of Science:
- Immunology
- Cell Biology
- Oncology
Background:
- MARCO, a scavenger receptor, is upregulated on tumor lysate-pulsed dendritic cells (DCs).
- MARCO expression influences DC morphology and migration.
- Targeting MARCO may enhance anti-tumor immune responses.
Purpose of the Study:
- To investigate the biological and therapeutic implications of MARCO expression on DCs.
- To evaluate the role of MARCO in DC migration and anti-tumor immunity.
Main Methods:
- Generated MARCO knockout (MARCO⁻/⁻) and wild-type DCs from bone marrow.
- Assessed DC phenotype, cytokine production (IL-12, TNF-α), and migratory capacity in vitro.
- Evaluated MARCO⁻/⁻ DCs in vivo for lymph node migration, T cell activation, and anti-tumor efficacy in B16 melanoma models.
Main Results:
- MARCO⁻/⁻ DCs exhibited normal phenotype and cytokine production.
- MARCO⁻/⁻ DCs showed enhanced migratory capacity towards CCL-21.
- In vivo, MARCO⁻/⁻ DCs migrated more efficiently to lymph nodes, boosting tumor-specific T cell responses, improving tumor regression, and increasing survival.
Conclusions:
- MARCO negatively regulates DC migration and anti-tumor immune responses.
- Targeting MARCO on DCs can improve their trafficking and enhance anti-tumor immunity.
- MARCO blockade represents a potential therapeutic strategy for cancer immunotherapy.
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