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Updated: Aug 25, 2026

Tumor Transplantation for Assessing the Dynamics of Tumor-Infiltrating CD8+ T Cells in Mice
Published on: June 12, 2021
Impact of tumor-derived CCL2 on T cell effector function
Peter F Vitiello1, Mara G Shainheit, Erin M Allison
1Department of Biology, Lafayette College, Easton, PA 18042, USA.
Abstract:
To study the effects of tumor-derived monocyte chemoattractant protein-1 (MCP-1, CCL2) on the anti-tumor immune response we used the 4T1 murine mammary carcinoma which constitutively expresses CCL2. We generated 4T1 that do not express detectable levels of CCL2 and found that the T cell response to the tumors were altered. Lymph nodes draining the CCL2- tumor contained CD62Llo cells that produced greater levels of INF-gamma in response to the tumor than CD62Llo cells from lymph nodes draining a tumor that produced CCL2. Moreover, exposure of splenic T cells to recombinant CCL2 in vitro decreased the ability of the T cells to produce IFN-gamma. However, despite the enhanced effector function evident in the absence of CCL2, vaccination/challenge experiments failed to reveal an increase in immunogenicity of the CCL2 null cells relative to the CCL2+ cells. Collectively, these data indicate that tumor-derived CCL2 could decrease T cell effector function, yet not the overall immunogenicity of the tumor.
Insights
Tumor-derived monocyte chemoattractant protein-1 (CCL2) can reduce T cell effector function. However, CCL2 does not impact the overall immunogenicity of the tumor, suggesting a complex role in anti-tumor immunity.
Area of Science:
- Immunology
- Cancer Biology
- Molecular Biology
Background:
- Monocyte chemoattractant protein-1 (MCP-1, CCL2) is a chemokine implicated in immune cell recruitment and function.
- Tumor-derived chemokines can modulate the anti-tumor immune response.
- The specific role of CCL2 in shaping T cell responses within the tumor microenvironment requires further elucidation.
Purpose of the Study:
- To investigate the impact of tumor-derived CCL2 on T cell responses and anti-tumor immunity.
- To determine if CCL2 influences T cell effector functions, such as cytokine production.
- To assess the effect of CCL2 on tumor immunogenicity in vivo.
Main Methods:
- Utilized the 4T1 murine mammary carcinoma model, generating CCL2-expressing and CCL2-null variants.
- Analyzed T cell populations and cytokine production (e.g., IFN-gamma) in draining lymph nodes.
- Exposed splenic T cells to recombinant CCL2 in vitro to assess direct effects on function.
- Conducted vaccination/challenge experiments to evaluate tumor immunogenicity.
Main Results:
- CCL2-null tumors altered T cell responses compared to CCL2-expressing tumors.
- CD62Llo T cells from lymph nodes draining CCL2-null tumors produced higher levels of IFN-gamma.
- In vitro exposure to CCL2 reduced the IFN-gamma production capacity of splenic T cells.
- Despite enhanced effector function in vitro, CCL2-null and CCL2-expressing tumors showed similar immunogenicity in vaccination/challenge models.
Conclusions:
- Tumor-derived CCL2 can suppress T cell effector function, specifically IFN-gamma production.
- CCL2 does not appear to significantly alter the overall immunogenicity of the tumor.
- These findings suggest that while CCL2 impacts T cell function, its role in determining tumor rejection is complex and may be compensated by other mechanisms.
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