The Ratio of GrzB+− FoxP3+ over CD3+ T Cells as a Potential Predictor of Response to Nivolumab in Patients with Metastatic Melanoma

The understanding of the molecular pathways involved in the dynamic modulation of the tumor microenvironment (TME) has led to the development of innovative treatments for advanced melanoma, including immune checkpoint blockade therapies. These approaches have revolutionized the treatment of melanoma, but are not effective in all patients, resulting in responder and non-responder populations. Physical interactions among immune cells, tumor cells and all the other components of the TME (i.e., cancer-associated fibroblasts, keratinocytes, adipocytes, extracellular matrix, etc.) are essential for effective antitumor immunotherapy, suggesting the need to define an immune score model which can help to predict an efficient immunotherapeutic response. In this study, we performed a multiplex immunostaining of CD3, FOXP3 and GRZB on both primary and unmatched in-transit metastatic melanoma lesions and defined a novel ratio between different lymphocyte subpopulations, demonstrating its potential prognostic role for cancer immunotherapy. The application of the suggested ratio can be useful for the stratification of melanoma patients that may or may not benefit from anti-PD-1 treatment.