The development of immune checkpoint inhibitors (ICIs) targeting lymphoid cells has remarkedly transformed therapeutic approaches for the treatment of cancer. However, response rates to TÂ 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.
