Researchers have identified a potential new target for immunotherapy capable of boosting the immune system at the same time as destroying cancer cells.

In a study undertaken at the Massachusetts General Hospital (MGH), a molecule called tumour necrosis factor receptor type II (TNFR2) was found to be a particularly effective target for destroying both immune system-suppressing and ovarian cancer cells.

TNFR2 is expressed on the surface of many types of cells within the body, including a type of cell which suppresses the immune system called regulatory T cells.

Past studies have shown that regulatory T cells can infiltrate tumours and suppress immune system activity around the site of the cancer, leading to the cancer ‘evading’ death incurred by immune cells.

“We have known for some time that TNFR2 is highly expressed in the tumour microenvironment, particular on the very important population of regulatory T cells, but we are now beginning to understand the potential efficacy of targeting cancer cells through the TNFR2 surface oncogene,” says Denise Faustman, corresponding author of the report and head of the Immunobiology Lab at MGH.

Faustman’s team made the discovery by exposing cancer cells to two manufactured antibody therapies that blocked the stimulation of TNFR2.

Initially, the antibody was investigated in the treatment of regulatory T cells isolated from fluid surrounding ovarian cancer tumours, as well as in a similar samples taken from cancer-free individuals. The antibody led to higher levels of regulatory T cell deaths in the ovarian cancer sample, suggesting that TNFR2-expressing regulatory T cells are unique to the tumour microenvironment.

The team then replicated the treatment’s effectiveness in TNFR2-expressing ovarian cancer cell samples.

Having both immuno-enhancing and cancer-killing capabilities makes the two TNFR2-suppressive antibodies a promising template for potential new immunotherapies targeting the molecule.

Xin Chen and Joost J. Oppenheim, both of the National Cancer Institute, commented on the study’s findings: “[The study] clearly shows that TNFR2 antagonists have promise as cancer therapies by simultaneously blocking both an immune checkpoint molecule in T cells and an oncoprotein in tumour cells.

“TNFR2 antagonists have the capacity to eliminate regulatory T cell activity and thus may further enhance the efficacy of current immunotherapeutics. In addition, suppression of tumour cell survival by the TNFR2 antagonist may improve the outcome of chemo- or radiotherapy in cancer patients.”

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