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Investigating the Link Between Tumor Vasculature Flow Dynamics and PD-L1 Upregulation

January 13, 2025 / by Lifeline® Cell Technology

National Blood Donor Month

January is National Blood Donor Month and a time to recognize the vital role of blood donation in patient care across a wide range of conditions. Beyond direct patient treatments, blood donors contribute to supporting research that improves our understanding of cancer onset and progression, as well as helping researchers develop novel therapies, including chimeric antigen receptor (CAR)-T cell therapies, which are revolutionizing the standard of care for blood cancers and hematological disorders.

Access to high-quality blood cells and culture media are essential for successful experimental execution. Lifeline® Cell Technology (LCT) has a diverse portfolio of blood cells and culture media to support critical oncology research. A recent study used LCT primary blood and endothelial cells to explore how the vascular dynamics of blood flow influence tumor-immune cell interactions, which could shed light into new targets for cancer immunotherapies.

Transmural Flow Upregulates PD-L1 Expression in Microvascular Networks

Tumor blood vessels have higher permeability than normal blood vessels, which exposes vascular endothelial cells (ECs) to elevated trans-endothelial (transmural) flow. Tumoral EC PD-L1 expression is also known to be upregulated. While PD-L1 upregulation allows cancer cells to evade immune responses, its link to transmural flow remains unclear. To investigate this, Wan and colleagues developed a microfluidic device to study PD-L1 expression in engineered microvascular networks (MVNs). The device generates transmural flow by separating a cell-free fibrin gel from an endothelial-stromal cell mixture that self-assembles into an MVN. Hydrostatic pressure differences drive fluid through the MVN or into the adjacent gel-filled channel to mimic tumor vasculature flow dynamics.

ECs in MVNs exposed to transmural flow for 24 hours showed increased PD-L1 expression, while stromal fibroblasts (FBs) did not, confirmed by immunostaining, qPCR, and flow cytometry. Both T cell extravasation and IFNγ secretion were suppressed in MVNs pretreated with transmural flow, highlighting a potential immune evasion mechanism.

Using a model of the tumor microenvironment in which PD-L1 expression had already been increased by cancer cells, the authors found that transmural flow further upregulated endothelial PD-L1 expression. To investigate the mechanism of transmural flow-induced PD-L1 upregulation in MVNs, blocking antibodies and knock-out (KO) assays were used. Blocking integrin αVβ3 abolished transmural flow-mediated PD-L1 upregulation in MVNs, and integrin αVβ3 KO was able to rescue T cell extravasation. These results demonstrate that integrin αVβ3 is critical for transmural flow-induced PD-L1 upregulation.

In summary, this study provides a new biophysical explanation for highly expressed PD-L1 in tumoral vasculatures, which can now potentially be targeted in novel treatments for cancer immunotherapy.

Lifeline Cell Technology Blood Cells and Media Products

Lifeline Cell Technology’s primary blood cells and optimized media products are used extensively for in vitro studies such as the one summarized here. They are ideal cell culture models for a wide range of applications from fundamental research to drug screening, to ensure the validity of research findings. Lifeline has a diverse array of blood cell products to further your research:

Visit us here at our blog to see our portfolio of human cells and culture media are helping researchers worldwide to answer scientific questions that drive new innovations.

If you have used our products to power your research, we’d love to feature your work here!

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