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Published in Science Advances: IsoPlexis’ Single-Cell Secretome Reveals Novel Targets Driving Tumor Immunosuppression

Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer, often correlated with poor patient outcomes due to its likelihood to metastasize and lack of druggable receptors. Though the use of immunotherapies has increased as treatment for various cancers, TNBC is still difficult to treat, with very few therapies finding success in targeting the disease for anticancer responses. Identifying effective drug targets is crucial to developing immunotherapies that elicit a stronger immune response against the tumor cells.

Investigating Novel Targets to Improve Therapeutic Efficacy with Single-Cell Functional Analysis

In a new study recently published in Science Advances, researchers at Emory University looked to identify novel targets for improving therapeutic efficacy against TNBC. Hypothesizing that breast cancer’s “immune-cold” property may be the reason current therapies continue to show poor patient outcomes, the researchers looked to CD73, a multifunctional enzyme overexpressed by aggressive TNBC cells that has been connected to poor prognosis in several other cancers. Using IsoPlexis’ IsoCode Single-Cell Secretome solution, the researchers investigated how CD73 affects T cell function by comparing two TNBC cell lines (wild-type TNBC and TNBC with modifications preventing CD73 degradation) with or without treatment of APCP (a CD73 inhibitor) when cocultured with CD8+ T cells.

With IsoPlexis’ Single-Cell Human Adaptive Immune assay, the researchers found that the mutated TNBC cell line that prevents the degradation of CD73 showed reduced polyfunctionality and PSI in CD8+ T cells compared to the wild-type TNBC line. They also found that, not only did treatment with APCP increase the polyfunctionality and PSI within the wild-type TNBC, but also recovered the polyfunctionality and PSI within the modified TNBC CD8+ T cells. These findings suggest that, because CD8+ T cells cocultured with the modified cells exhibited lower polyfunctionality and PSI compared to the wild type, CD73 actively suppresses immune function within TNBC and thus could be a valuable target for developing more effective therapies against the disease.

Single-Cell Functional Proteomics Reveals Unique Insights into Tumor Resistance

This study demonstrates how single-cell functional analysis allows researchers to investigate and uncover unique insights into the mechanisms driving tumor resistance and immunosuppression. By gaining a deeper understanding of how immune cells interact with tumor cells, researchers can continue to develop better therapies that increase the effectiveness of immunotherapy, leading to more positive clinical outcomes.

Learn more about how IsoPlexis’ single-cell functional proteomics is being used to reveal interactions between tumors and the immune system: IsoPlexis Proteomic Product Suite for Cancer Immunology | IsoPlexis

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