Immunological phenotype as a predictor for response after isolated limb perfusion for patients with melanoma in-transit metastasis

Background Isolated limb perfusion (ILP) is a regional treatment for patients with melanoma in-transit metastases (ITM) confined to extremities. Reported complete response (CR) rates for ILP varies but is approximately 50–70 %. This study aims to analyze if specific immunological phenotypes could predict CR after ILP. Methods 132 patients undergoing ILP as a first treatment for melanoma ITM between January 2012 and March 2023 were included. The number and percentage of naïve and memory T and B cell subtypes, and natural killer (NK) cells, were characterized by analyzing pre-operative blood sample using fluorescence activated cell sorting (FACS). Predictive clinical and immunological factors for CR after ILP were analysed using univariable and multivariable analysis. Results Response was evaluable in 119 patients (90 %), of which 53 % achieved a CR. After adjusting for age, sex, number of metastases and size of the largest metastasis, immunological factors independently associated with a CR, were percentage of cytotoxic T cells (CD3 + 8 + ) (OR 1.07, 95 % CI 1.02–1.13, p = 0.012) and percentage of naive cytotoxic T cells (CD3 + 8 + 45RA + ) (OR 1.11 95 % CI 1.01–1.22, p = 0.029). Conclusion Immunological phenotype described as percentage of cytotoxic T cells and naïve cytotoxic T cells are together with tumor burden important predictive factors for response after ILP for patients with melanoma ITM. This could contribute to better patient selection, individualized treatment algorithms and be a foundation for further research into systemic immunological effects of regional cancer therapies. This includes novel treatment combinations, where an ongoing trial is currently combining ILP with a PD-1 inhibitor (ClinicalTrials.gov NCT03685890).