Vestibular schwannomas are a type of rare noncancerous tumor that grow on the eighth cranial nerve, causing hearing loss, balance issues, and facial weakness or paralysis. If untreated, VS tumors can grow large enough to become life-threatening. VS tumors grow at an unpredictable rate, making it difficult to know what the best treatment options are. Surgical removal of the entire tumor is often impossible due to the tumor’s proximity to other parts of the nervous system, and incomplete removal has been linked to tumor progression and decreased survival rates. Unfortunately, researchers still do not fully understand the biological mechanisms that cause some VS tumors to recur and progress while others do not.
Characterizing how VS cells interact with the immune system can provide clues about mechanisms of tumor progression. Immune cells have a wide range of functions, even those of the same cell type, making it difficult to fully characterize cells in a heterogeneous population. Analytical techniques that average across cells can miss changes in specific subsets of immune cells. However, IsoPlexis’ IsoCode® Single-Cell Secretome solution provides a platform that can assess the function of individual cells across a population of thousands at once, giving researchers deeper insights into immune cell function and subsets of cells driving immune responses.
Uncovering Mechanisms of Tumor Progression with Single-Cell Functional Analysis
A new study recently published in the Journal of Experimental & Clinical Cancer Research used single-cell functional analysis to investigate how VS tumor cells interact with the immune system and create a microenvironment that allows for tumor progression. The researchers first noticed a difference in the types of immune cells associated with rapidly or slowly progressing VS tumors, with the rapidly progressing tumors containing increased CD4+ and CD8+ T cells. Counterintuitively, transcriptome analysis of tumor-associated immune cells from rapidly progressing VS tumors showed that pathways associated with immune response were significantly lower, suggesting that there was dysfunction in the adaptive immune response.
To better understand and characterize this dysfunction, the researchers used IsoPlexis’ IsoCode® Single-Cell Secretome platform to investigate how VS tumor cells affect T cell function. CD3/CD28 activated mouse CD8+ T cells were incubated with a mouse VS cell line, with other activated CD8+ T cells incubated alone used as a control. The functional cytokine secretions of individual CD8+ T cells in both groups were measured and used to create a t-SNE, which graphically collapses high-dimensional data to visualize differences between groups. The t-SNE showed that CD8+ T cells incubated alone and those incubated with VS cells formed two discrete groups, indicating that the immune cells had functionally distinct cytokine secretion profiles.
Next, the researchers assessed the number of polyfunctional cells (cells secreting two or more cytokines) and PSI (polyfunctional strength index), in each group. Polyfunctional cells are a small subset of immune cells that have been shown to drive immune response, making them a powerful predictor of immune activity. The researchers found that the CD8+ T cells incubated with VS tumor cells had lower PSI and fewer polyfunctional cells than those incubated alone, with the co-incubated T cells secreting fewer effector, chemoattractive, inflammatory, and stimulatory cytokines. Together, these results demonstrate that VS tumor cells suppress CD8+ T cell function, generating a tumor immune microenvironment that allows for tumor progression. Single-cell functional analysis provided the level of detailed information needed to better to understand how VS cells affect immune function and give researchers an idea of how to counteract it to improve VS treatments.
Single-Cell Functional Proteomics is Driving Novel Discoveries
This study demonstrates how single-cell functional analysis can lead to unique insights into the interaction between tumor and immune cells, helping to shed light on mechanisms that lead to tumor progression and worse clinical outcomes. By gaining a deeper understanding of individual cell function within a population, researchers can make new discoveries and identify novel targetable pathways. Single-cell functional analysis is being used across a wide range of applications to advance human health and create better therapies.
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