Enhancing Immune Cell Function and Reshaping the Tumor Microenvironment Through CCR2 Inhibition
Presenter Status
Staff
Abstract Type
Translational Research
Primary Mentor or Principal Investigator
John Perry
Presentation Type
Poster
Start Date
19-5-2026 11:00 AM
End Date
19-5-2026 12:00 PM
Abstract Text
Background: The tumor microenvironment (TME) is a complex environment in which non-cancerous stromal and immune cells support tumor progression and metastasis. Among these, tumor associated macrophages (TAMs) can constitute up to half of the immune cell population within solid tumors and frequently polarize toward an anti-inflammatory M2 phenotype capable of suppressing anti-tumor immunity. The chemokine receptor CCR2, which is expressed on macrophages, is known to be involved in cellular chemotaxis and regulates their recruitment into tumors. It has also been implicated in macrophage polarization, although the underlying mechanisms remain unclear. Notably, inhibition of CCR2 signaling has been shown to enhance anti-tumor responses when combined with anti-PD-1 therapy, suggesting that inhibition of CCR2 may promote a shift toward a pro-inflammatory, immunostimulatory TME.
Chimeric antigen receptor (CAR) T cell immunotherapy, while highly effective against hematologic malignancies, has demonstrated limited efficacy in solid tumors due to poor trafficking and immunosuppression within the TME. Engineering CAR T cells to express chemokine receptors that respond to tumor secreted signals represents a promising strategy to improve infiltration into solid tumors. CXCR5, which mediates chemotaxis toward CXCL13, is of particular interest because CXCL13 is overexpressed across numerous solid tumor types. Thus, CAR T cells expressing CXCR5 may exhibit enhanced trafficking to a broad range of CXCL13 producing tumors.
Objectives: We are currently initiating studies to evaluate combination therapies integrating CXCR5 engineered CAR T cells with CCR2 pathway inhibition. We hypothesize that CXCR5 expression will improve CAR T cell recruitment to CXCL13 secreting tumors, while CCR2 inhibition will reshape the TME and promote conditions more favorable to CAR T cell function. Additionally, we aim to elucidate the mechanisms through which CCR2 signaling regulates macrophage behavior and broader immune activity within the TME. Together, these studies will advance understanding of how TME modulation can synergize with CAR T cells to improve solid tumor immunotherapy.
Enhancing Immune Cell Function and Reshaping the Tumor Microenvironment Through CCR2 Inhibition
Background: The tumor microenvironment (TME) is a complex environment in which non-cancerous stromal and immune cells support tumor progression and metastasis. Among these, tumor associated macrophages (TAMs) can constitute up to half of the immune cell population within solid tumors and frequently polarize toward an anti-inflammatory M2 phenotype capable of suppressing anti-tumor immunity. The chemokine receptor CCR2, which is expressed on macrophages, is known to be involved in cellular chemotaxis and regulates their recruitment into tumors. It has also been implicated in macrophage polarization, although the underlying mechanisms remain unclear. Notably, inhibition of CCR2 signaling has been shown to enhance anti-tumor responses when combined with anti-PD-1 therapy, suggesting that inhibition of CCR2 may promote a shift toward a pro-inflammatory, immunostimulatory TME.
Chimeric antigen receptor (CAR) T cell immunotherapy, while highly effective against hematologic malignancies, has demonstrated limited efficacy in solid tumors due to poor trafficking and immunosuppression within the TME. Engineering CAR T cells to express chemokine receptors that respond to tumor secreted signals represents a promising strategy to improve infiltration into solid tumors. CXCR5, which mediates chemotaxis toward CXCL13, is of particular interest because CXCL13 is overexpressed across numerous solid tumor types. Thus, CAR T cells expressing CXCR5 may exhibit enhanced trafficking to a broad range of CXCL13 producing tumors.
Objectives: We are currently initiating studies to evaluate combination therapies integrating CXCR5 engineered CAR T cells with CCR2 pathway inhibition. We hypothesize that CXCR5 expression will improve CAR T cell recruitment to CXCL13 secreting tumors, while CCR2 inhibition will reshape the TME and promote conditions more favorable to CAR T cell function. Additionally, we aim to elucidate the mechanisms through which CCR2 signaling regulates macrophage behavior and broader immune activity within the TME. Together, these studies will advance understanding of how TME modulation can synergize with CAR T cells to improve solid tumor immunotherapy.
Comments
Restricted to Title/Author List/Abstract only as requested by primary author
Poster Board Number: 33