Novel Method for Predicting Immunotherapy Response in Melanoma Patients

A recent study shows that macrophages can be used to predict whether or not a melanoma patient will respond to chemotherapy. The results were published in Oncology Advances.

While immunotherapy is a potent treatment for many forms of cancer, unfortunately only around half of patients respond to this type of treatment. Therefore, selecting the optimal therapy is often a trial-and-error process.

In this study, researchers from the Universities of Bath (UK) and Stanford University (CA, USA), examined novel biomarkers that may be utilized to identify melanoma patients more likely to respond to TVEC immunotherapy, which is a modified oncolytic virus that is injected into melanoma directly to induce an immune response. While TVEC has previously be used in advanced melanoma, this study was the first to examine its potential to treat high-risk stage II melanoma patients.

Researchers believed that TVEC worked by activating T cells, causing them to attack the cancer cells and shrink the melanoma. However, this novel research uncovered that pre-existing and post-treatment T cell populations did not have association with treatment responses. Rather changes in the macrophage were linked to which patients responded to immunotherapy versus those which did not.

Specifically, the researchers used a method called iFRET, which monitors protein activation rather than protein amount. The findings showed found that T cell presence showed no consistent trends to viral stimulation or tumor response before and after the treatment, but there was a heavy infiltration of macrophages after treatment in responding patients, associated with very high activation across immune checkpoint regulators. Researchers will now aim to develop clinically predictive tests of which patients will respond to immunotherapy, which in turn will enable clinicians to tailor a personalized treatment.

Professor Banafshé Larijani, Department of Life Sciences and Director of the Centre for Therapeutic Innovation at the University of Bath, co-leader of the study said: “We know that people respond to immunotherapy very differently – in some cases the tumors shrink, and in others, sadly the patients do not survive. Our findings show that it’s not enough to simply look at T cell activity, instead it’s imperative to look at the whole immune response environment in detail to predict how a patient will respond to different treatments.”