Within the cancer immunology space, single cell innate and myeloid cell-based assays have gained considerable attention as targets for drug delivery, and have been recognized as major players in the field. Monocytes/macrophages are key players in the tumor microenvironment and have been known to modulate effector T cell activity. While many studies have demonstrated that monocytes have a brief and weak anti-tumor response and instead exhibit immunosuppressive and pro-tumor roles, other evidence suggests that monocytes/macrophages could produce a heterogeneous response. The ideal goal of a monocyte-specific assay is to understand the sources of immune suppression directly from single cell macrophage functionality, both circulating and tumor associated macrophages (TAMs), and to then identify how to tune those suppressor cells with a variety of small molecules, or immunomodulators, to increase the potential of T cells engaging the tumor.
While it is known that the ability to see and multiplex the true protein secretions from single cells is critical in developing and optimizing various types of immunotherapies, the technologies that many researchers currently use (flow cytometry, bulk ELISA, RNA-Seq, etc.) cannot provide this type of highly multiplexed data because they rely on estimates of single-cell cytokine production. IsoPlexis is able to reveal the direct and true single-cell functional phenotype via secreted cytokines. With the new Single-Cell Innate & Myeloid solution, IsoPlexis can deliver single-cell-level data while allowing researchers to visualize differences in an innate/myeloid-centric way. By understanding the functional phenotype of innate and myeloid cells, researchers can pinpoint biological drivers of immune response within the tumor microenvironment. This Single-Cell Innate & Myeloid solution runs on the revolutionary, award-winning IsoLight proteomic hub, which enables researchers to plug into their development pipeline.
The Single-Cell Innate & Myeloid Panel is empowering researchers by:
- Providing a fully automated and integrated, end-to-end process and system (runs on the IsoLight), unleashing true functional biology for innate & myeloid cell biomarkers
- Uniquely revealing functional sources of immune suppression from rare subsets of immune cells
- Detecting functional cellular differences that correlate to immune suppression
- Utilizing single cell innate & myeloid data for translational insights to advance discovery and development programs by revealing the sources of cellular differences based on the ability to detect what each immune cell is truly secreting in a highly multiplexed manner
Detecting the Functional Cellular Differences that Correlate to Immune Suppression
Data generated using IsoPlexis’ Innate & Myeloid panel was shown in a recent publication in Blood Cancer Journal. The study showed that CD14+SIRPαhi (signal regulatory protein-α) monocytes/macrophages (Mo/MΦs) were associated with inferior survival in follicular lymphoma (FL) and increased numbers of the CD14-SIRPαlow subset appeared to correlate with better survival. Unique subsets of intratumoral monocytes/macrophages have differing prognostic importance. Unique mechanisms displayed by the IsoPlexis platform, and in particular, the Single-Cell Innate & Myeloid panel, show monocyte functionality plays a key role in the progression of FL.
Importance of Monocyte/Macrophage Cellular Polyfunctionality
Key findings of the Blood Cancer Journal publication, enabled by the Innate & Myeloid solution:
- An inhibitory mechanism of enhanced IL-10 in single-cell polyfunctional CD14+SIRPαhi subsets for T cell proliferation, which provides the functional insights of Mo/MΦ subsets for FL patients, which were implicated in inferior survival of patients.
- In this case, the cellular IL-10 level shows critical mechanistic importance of monocyte function in the interaction with T cell functional response, which correlated with patients who had inferior survival.
- A positive correlation of polyfunctionality of monocyte subsets, in particular the CD14+SIRPαhi, to phagocytic capacity of Mo/MΦ subsets enhanced by the SIRPα/CD47 blockade, a promising tumor immunotherapy targeting innate immunity.
- Researchers were again able to display correlative polyfunctional capacity to phagocytosis, providing insight in two related mechanisms for the overall response that resulted in inferior survival of patients.
- Significant polyfunctional heterogeneity with inflammatory cytokine/chemokine signatures, in the 3 cell subsets of CD14+SIRPαhi, CD14-SIRPαlow, and CD14-SIRPαneg monocytes/macrophage in FL patients, which led to the discovery of significant differences between these subsets, which correlated to the progression of FL.
As demonstrated in the study above, IsoPlexis’ single cell innate and myeloid readouts are helping to prove out the mechanisms of tumor immune suppression, CNS, and autoimmune diseases by highlighting clear differences that would be undetectable with bulk or flow assays. These differences give researchers the confidence they need to accelerate their decision making and the edge over their competition when bringing immunotherapies to market.
Leaders all over the world are using IsoPlexis’ highly differentiated platform to overcome the challenges in cancer immunology. When translating from late discovery to phase 1, it’s imperative to know the subtle, but critical single cell innate and myeloid contributions that can provide the necessary information for your therapy programs. IsoPlexis’ revolutionary immune cell functional biology is the only technology that can provide this information. IsoSpeak software, part of the IsoLight proteomic hub, automatically analyzes data from each chip and quickly produces various advanced visualizations that researchers can use to gain a full understanding of deep functional cellular insights. The single-cell mapping tools within the software suite are easily accessed via a push-button user interface for accelerated same-day data analysis.
To learn more about the new Single-Cell Innate & Myeloid solution, download the product sheet.