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Updated: Aug 2, 2025
In Vitro Assay to Study Tumor-macrophage Interaction
Published on: August 1, 2019
Macrophage CD5L is a target for cancer immunotherapy
Lidia Sanchez-Moral1, Tony Paul1, Clara Martori2
1Innate Immunity Group, Germans Trias i Pujol Research Institute (IGTP), 08916 Badalona, Spain.
Background:
Reprogramming of immunosuppressive tumor-associated macrophages (TAMs) presents an attractive therapeutic strategy in cancer. The aim of this study was to explore the role of macrophage CD5L protein in TAM activity and assess its potential as a therapeutic target.
Methods:
Monoclonal antibodies (mAbs) against recombinant CD5L were raised by subcutaneous immunization of BALB/c mice. Peripheral blood monocytes were isolated from healthy donors and stimulated with IFN/LPS, IL4, IL10, and conditioned medium (CM) from different cancer cell lines in the presence of anti-CD5L mAb or controls. Subsequently, phenotypic markers, including CD5L, were quantified by flow cytometry, IF and RT-qPCR. Macrophage CD5L protein expression was studied in 55 human papillary lung adenocarcinoma (PAC) samples by IHC and IF. Anti-CD5L mAb and isotype control were administered intraperitoneally into a syngeneic Lewis Lung Carcinoma mouse model and tumor growth was measured. Tumor microenvironment (TME) changes were determined by flow cytometry, IHC, IF, Luminex, RNAseq and RT-qPCR.
Findings:
Cancer cell lines CM induced an immunosuppressive phenotype (increase in CD163, CD206, MERTK, VEGF and CD5L) in cultured macrophages. Accordingly, high TAM expression of CD5L in PAC was associated with poor patient outcome (Log-rank (Mantel-Cox) test p = 0.02). We raised a new anti-CD5L mAb that blocked the immunosuppressive phenotype of macrophages in vitro. Its administration in vivo inhibited tumor progression of lung cancer by altering the intratumoral myeloid cell population profile and CD4+ T-cell exhaustion phenotype, thereby significantly modifying the TME and increasing the inflammatory milieu.
Interpretation:
CD5L protein plays a key function in modulating the activity of macrophages and their interactions within the TME, which supports its role as a therapeutic target in cancer immunotherapy.
Funding:
For a full list of funding bodies, please see the Acknowledgements.
Insights
Targeting CD5L protein in tumor-associated macrophages (TAMs) can reprogram the immunosuppressive tumor microenvironment (TME). This study demonstrates CD5L
Area of Science:
- Immunology
- Oncology
- Biochemistry
Background:
- Reprogramming immunosuppressive tumor-associated macrophages (TAMs) is a promising cancer therapy.
- The role of macrophage CD5L protein in TAM activity and its therapeutic potential require exploration.
Purpose of the Study:
- To investigate the function of macrophage CD5L protein in TAMs.
- To evaluate CD5L as a potential therapeutic target in cancer immunotherapy.
Main Methods:
- Generated anti-CD5L monoclonal antibodies (mAbs).
- Assessed macrophage phenotype in vitro using flow cytometry, IF, and RT-qPCR.
- Quantified CD5L expression in human lung adenocarcinoma (PAC) samples.
- Evaluated anti-CD5L mAb efficacy in a murine lung cancer model, analyzing tumor growth and TME changes.
Main Results:
- Cancer cell-conditioned medium induced an immunosuppressive macrophage phenotype, including increased CD5L expression.
- High CD5L expression in PAC TAMs correlated with poor patient outcomes.
- In vitro, anti-CD5L mAb blocked macrophage immunosuppression.
- In vivo, anti-CD5L mAb inhibited tumor progression by modulating myeloid cells and T-cell exhaustion, enhancing the inflammatory TME.
Conclusions:
- CD5L protein is crucial for macrophage activity and TME modulation.
- CD5L represents a viable therapeutic target for cancer immunotherapy.
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