Leveraging AIM’s BioAvatar technology to tackle previously-unknown effects of immune protein ligands in tumors

Although immune checkpoint protein PD-1 activation is known to participate in tumor development and to inhibit adoptive T cell therapy effects, the expression of its ligand PD-L1 during oncogenesis progression is not well understood. A group of scientists studied the mechanism of PD-L1 expression and PD-1 activation in pancreatic ductal adenocarcinoma (PDA) to better understand T cell behaviour during cancer progression.

Examining PD-L1 expression in a PDA mouse model and human patients

In work published in Nature Immunology in 2020, scientists showed that PD-L1 expression increased together with tumor progression in a mouse model of PDA.

The authors found that in human PDA, PD-L1 was highly expressed in infiltrating T cells in tumor tissues. Also, PD-L1 was present in about 50% of pancreatic T cells, while minimal expression was found in healthy pancreas tissue.

To study PD-L1 expression consequences on T cell activity, scientists applied PD-1 Fc (a chimera of PD-1 protein with a fragment crystallizable region to allow the protein to bind the cells) to human T cells in vitro. After three days of treatment, they analysed the expression of immune markers with the RNA-Seq sequencing technique. They found that PD-1 activation downregulates the expression of genes associated with the immunogenic response.

Harnessing AIM Biotech BioAvatar technology using idenTx chips to study PD-1/PD-L1 signaling

To study PD-L1 effects on a human-like tumor model, the authors used AIM Biotech’s idenTx chip to grow tissue spheroids obtained from human patient PDA biopsies. The spheroids were injected into the central chamber of the idenTx chip and treated with PD-1 Fc, or IgG Fc as a control. They found that spheroids treated with PD-1 Fc demonstrated accelerated cell growth compared to the control condition. Also, the treatment suppressed intra-tumoral T cell phenotype, highlighting the role of PD-L1 binding to T cells as a tumor-promoting tolerogenic effector.

The easy-to-implement and cost-effective human-like tumor model developed for this study was made possible by leveraging AIM Biotech’s idenTx chips and BioAvatar technology, enabling scientists to study previously unknown impacts of PD-L1 expression on T cell populations.

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*PD-L1 engagement on T cells promotes self-tolerance and suppression of neighboring macrophages and effector T cells in cancer. Diskin, B., Adam, S., Cassini, M.F. et al. Nat Immunol 21, 442–454 (2020). https://doi.org/10.1038/s41590-020-0620-x