Phosphatidylserine (PS) is a small molecule mainly found at high levels on the outer membrane of dying cells, from where it is known to promote an immunosuppressive microenvironment in tumors through its interaction with its receptors. A study led by Ludwig MSK researchers Taha Merghoub, Sadna Budhu and Jedd Wolchok published in Cell Reports in January found expression of PS on live tumor-infiltrating immune cells rises after a single dose of radiation delivered to melanoma tumors in mice. The researchers found that PS-blockade with the antibody mch1N11 enhanced the effects of radiotherapy and extended survival of the mice. The effect was accompanied by an increase in the proportion of pro-inflammatory macrophages and an increase in the recruitment and activation of T cells in tumors. Adding anti-PD-1 checkpoint blockade immunotherapy to the mix further enhanced T cell activation, responses to radiotherapy and survival of the mice. The researchers also showed that immune cells in the blood of melanoma patients who have received radiotherapy similarly express higher levels of PS. These findings suggest that patients could benefit from the concurrent blockade of PS and PD-1 in combination with radiotherapy.
This article appeared in the April 2021 issue of Ludwig Link. Click here to download a PDF (1.4 MB).