In this last article of the immune checkpoint series, we discuss how scientists used AIM Biotech’s Avatar technology to study when, how, and which cells express the PD-L1 immune protein in breast cancer.
PD-L1 expression promotes tumor growth by offering an invasive behaviour to cancer cells. It’s believed that the tumor microenvironment contributes to PD-L1 expression, mainly by its expression in mesenchymal cells. A work published in the Journal of Cellular Physiology in 2020, showcases the use of AIM Biotech’s idenTx chip to study PD-L1 expression in a model of human breast cancer.
Do mesenchymal cells contribute to invasive cell behavior?
To address this question, the scientists first incubated human breast adenocarcinoma cells, MCF7, into the idenTx chips. They treated the MCF7 cells with a conditioned cell medium obtained from the culture of human adipose‐derived mesenchymal cells. Consequently, the conditioned medium contains molecules released by mesenchymal cells.
After incubating with the conditioned medium or with a regular medium (control), the authors stained the MCF7 cells contained in the chips. They discovered that the presence of conditioned medium produces a higher expression of a mesenchymal cell marker and a lower expression of an endothelial cell marker than the control condition.
Do mesenchymal cells promote PD-L1 expression?
Later, to better understand the mechanism of PD-L1 expression, the authors formed multicellular aggregates (MCA) from cultured MCF7. These MCAs were injected into the central chamber of the idenTx chip and treated with regular cell medium (control condition) or the conditioned one. After 3 days of incubation, the scientists did immunostaining on the tissue inside the chip to search for endothelial and mesenchymal markers. Again, they found a higher expression of mesenchymal markers in the conditioned medium condition. Also, they searched for PD-L1 expression and found a higher expression in the sample treated with the conditioned medium.
Does cytokine release promote PD-L1 expression?
To understand how mesenchymal cells promote PD-L1 expression, the authors collected the cell medium and measured its cytokine concentration. They found that, remarkably, CCL5 was increased in the sample treated with conditioned medium. Suspecting that cytokine release promotes PD-L1 expression, the scientist incubated the MCA treated with conditioned medium with pirfenidone (PFD), a known cytokine expression inhibitor. As expected, the treatment with PFD decreased the CCL5 production and, consequently, the PD-L1 expression.
Thanks to AIM Biotech’s idenTx chip, scientists deciphered how PD-L1 is expressed in cancer cells: it depends on mesenchymal cells release of cytokines, suggesting an alternative approach for cancer immunotherapy in a combination manner.
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