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

Simple Summary Despite the recent success of immunotherapy in the treatment of malignant melanoma, many patients still do not benefit from these treatments, due to their failure to activate an antitumor immune response them. There is therefore a need to select patients who can truly benefit from these treatments. We have focused our study on immune cells present in the tumor microenvironment, and we have developed a formula (ratio) that correlates with the response to anti-PD1 therapy and progression-free and overall survival, based on the numerical difference between GRZB(+) and FOXP3(+) cells over the total CD3(+) lymphocytes. This developed ratio could be useful to better select patients that may or may not benefit from anti-PD-1 treatment. 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.

Automated summary

This study focuses on immune cells within the tumor microenvironment and has developed a ratio that correlates with response to anti-PD1 therapy. The developed ratio may help in better patient selection for the treatment.