Conniving Cancer Cells: How scRNA-seq Uncovers Stromal Plasticity in Tumors

March 23, 2022

What are Stromal Cells?

A key component of the tumor microenvironment is the stromal cell. Stromal cells refer broadly to the structural cells of the tumor that are neither cancer cells nor immune cells.

Cellular structure is a very tightly controlled process and involves proteins and transcription factors that comprise the extracellular matrix (ECM), a structural network around and between cells. In order to proliferate at a rapid and unnatural pace, tumors undergo significant remodeling of the ECM to make room for more cancer cells, a process that the body attempts to combat.

The Role of Stromal Cells in Cancer Treatment Response

With the importance of these structural elements in mind, and the many conflicting molecular interactions occurring between stromal cells and the body’s defenses against cancer progression, it makes sense that stromal cells would play a large role in determining the microenvironment of a tumor. As such, they will affect the efficacy of any cancer treatment, from a pharmacological agent to an immunotherapy.

Using scRNA-seq, we can begin to uncover the full complexity of stromal cells, and their influence on cancer progression. Understanding this process will be critical for continuing to develop effective precision treatments for cancer.

scRNA-seq Uncovers New Therapeutic Target

A recent Nature Communications paper by a Novartis research team used scRNA-seq to examine the subpopulations of stromal cells, and their response to blocking a critical transcription factor for ECM remodeling, TGFβ. What they found is that stromal cells are highly dynamic in response to stress.

Intriguingly, they found that blocking TGFβ had a significant effect on stromal cell and ECM remodeling that allows for an improved anti-tumor response by the immune system. Treatment with PD1 immunotherapy, a gold-standard approach in current cancer treatments, was more effective when TGFβ was blockaded. Excitingly, these studies were done in vivo in a mouse model, providing strong evidence for co-blockade of PD1 and TGFβ to be tested in humans.

Harnessing the Power of scRNA-seq and Outsourcing Bioinformatic Analysis

scRNA-seq is an extremely powerful analysis technique for understanding dynamic, heterogeneous cell populations, like those of a tumor. This study on the relatively poorly-understood stromal environment in the cell identified unique cell subpopulations and how they change in response to different treatments, leading to a new therapeutic target strategy for human cancer treatment.

Processing and analyzing scRNA-seq data is a complex computational task. Outsourcing your bioinformatic work can save time, eliminate common challenges, and improve reproducibility. Book a free discovery call with us at Bridge Informatics to discuss your project needs.

Jane Cook, Journalist & Content Writer, Bridge Informatics

Jane is a Content Writer at Bridge Informatics, a professional services firm that helps biotech customers implement advanced techniques in management and analysis of genomic data. Bridge Informatics focuses on data mining, machine learning, and various bioinformatic techniques to discover biomarkers and companion diagnostics. If you’re interested in reaching out, please email or


Red liquid being pipetted into a PCR plate for analysis and downstream bioinformatic processing

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