Researchers at the Netherlands Cancer Institute have discovered a cluster of melanoma tumour cells that are refractory to immunotherapy and exist even before treatment.
In a paper published in Nature Communications, the team present a study of melanoma cells cultured from patients exposed to T cells. After repeated exposure, the surviving tumour cells were not only fully resistant to T cells, but they also expressed high amounts of nerve growth factor receptor (NGFR). Areas of high NGFR expression were often much less infiltrated with T cells than regions with low NGFR expression.
NGFR-expressing melanoma cells were also resistant to BRAF and MEK inhibitors, and were more refractory to chemotherapy and irradiation.
When expression of NGFR was suppressed, cultured melanoma cells were re-sensitised to T cells.
Melanoma-bearing mice also survived longer when NGFR was inhibited during immunotherapy.
The findings suggest NGFR may be an attractive therapeutic target to be used in combination with immunotherapy.
There are no NGFR precision medicines available as yet, but co-author, Daniel Peeper said, an appealing option would be to use the cell membrane localisation of NGFR to target it with an antibody.