New research identified cellular connections that are fundamental to the immunological response to ovarian cancers

Nov, 2021 - By WMR

A study by Ludwig Cancer Research institute revealed a cellular interaction required for the immune system's cytotoxic T lymphocytes to eliminate ovarian tumors and demonstrated that its activation could assist examine the efficiency of checkpoint blockade immunotherapy in various cancers.

The study reveals how cancer-killing infiltrating T lymphocytes (TILs) dwell in islets within ovarian tumors. These islets also include immune cells called antigen-presenting cells (APCs). In cell culture and mouse tests, the researchers reveal that APCs, which help lead TILs to cancer cells and promote their activity, trigger a protein on TILs known as CD28 to boost and sustain their effectiveness. This interaction licenses TILs to target tumor cells when they are controlled with anti-PD-1 checkpoint blockade antibodies, which release the brakes placed on TIL function.

In 2003, a study performed by Ludwig Lausanne Director George Coukos demonstrated that ovarian tumors with the highest TIL infiltration have the longest patient survival periods. Furthermore, cancer like the majority of others has proven to be reasonably resistant to anti-PD-1 checkpoint blockade treatment.

Coukos and his colleagues investigated this phenomenon by profiling TILs from specimens of high-grade serous ovarian cancer, the most prevalent and aggressive type of the illness. They discovered the most effective anti-tumor TILs were detected in tumor islets rather than at the tumor's periphery. TILs in these tumors, they illustrate, exist in a range of states, from engaged and ready to attack to various degrees of exhaustion and terminally exhausted, a condition of permanent ineffectiveness.

TILs most equipped to target tumors engage in a two-way connection within the islets, activating cancer antigens with their specific receptors on the one hand, and APCs like dendritic cells and macrophages on the other. The researchers also discovered that the most capable TILs express the PD-1 molecule, which inhibits their tumor-targeting function. The anti-PD-1 checkpoint blockage disengages that brake.

In experiments on mice implanted with ovarian tumors, the researchers found that combining the three medicines resulted in significantly better tumor control in the animal model than either single or dual therapy. As the medicines investigated in this study are already widely used or in clinical studies, the study results might be subjected to clinical review very soon.