License to kill

A study led by Ludwig Lausanne Director George Coukos uncovered a cellular interaction essential to the ability of the immune system’s cytotoxic T lymphocytes to destroy ovarian tumors in response to immunotherapy. George and his colleagues reported in a November issue of Cancer Cell that infiltrating T lymphocytes (TILs) best able to kill cancer cells reside in islets within ovarian tumors. These islets additionally house antigen presenting cells (APCs), like dendritic cells and macrophages, which support TIL activity. The APCs stimulate a protein, CD28, on TILs to boost and sustain their functionality. George and his team showed that TILs activated by PD-1 blockade have to be simultaneously stimulated by APCs through CD28 to be effectively licensed to kill cancer cells. The researchers showed that adding a stimulator of APCs, known as CD40L, in combination with anti-PD-1 and anti-CTLA-4 checkpoint blockade therapies restored the anti-tumor activity of unresponsive TILs in cell cultures. Testing this approach in studies on mice implanted with ovarian tumors, George and his colleagues demonstrated that a combination of the three therapies resulted in much better tumor control in the mouse model than did either single or dual therapy. Their data also show that the identified mechanism is likely to be of relevance in many other cancers as well.

This article appeared in the February 2022 issue of Ludwig Link. Click here to download a PDF (1 MB).


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