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Immune checkpoint inhibitors and MDSCs

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Dr Andreia Soares

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Dr Andreia Soares

The development of immune checkpoint inhibitors (ICIs) targeting lymphoid cells has remarkedly transformed therapeutic approaches for the treatment of cancer. However, response rates to T cell checkpoint inhibitors vary between individuals with some patients showing minimal to no clinical benefit. In these patients, resistance to this immunotherapy may be partly attributed to myeloid- derived suppressor cells (MDSCs), a heterogeneous population of myeloid progenitors and immature myeloid cells that function as immune suppressors.

An article published in Nature Cancer by Li and colleagues (https://www.nature.com/articles/s43018-020-0061-3) shows that c-Rel, a NF-κB family member, plays a key role in the development of MDSCs and in modulating MDSC regulated anti-tumour immune responses. It was shown that inhibiting c-Rel in myeloid cells blocked the differentiation of MDSCs, significantly inhibited tumour growth and enhanced T cell checkpoint blockade–mediated anti-tumour responses in a murine model. In vitro, human MDSCs generated in the presence of a c- Rel inhibitor had significantly reduced suppressive activity on CD8+ T cell proliferation and reduced expression of the MDSC signature messenger RNAs ARG1 and CEBPB. These results identify c-Rel and MDSCs as a promising immunotherapeutic target for lymphoid ICI non-responsive patients and as a combination therapy.

Synexa Life Sciences has established flow cytometry panels to characterise circulating MDSC subsets and determine the effects of MDSC-targeting therapeutics. We also offer a range of panels to assess T cell functional profiles (cytokine production and proliferation) to support clients in pre-clinical and clinical immuno-oncology research.

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