Heterogeneity of CD8 T-Cell Changes in Advanced Melanomas After Initiation of Immunotherapy

Whole-body CD8+ T-cell PET imaging can detect spatial and temporal localization of CD8+ T cells. To obtain insight into early CD8+ T-cell response to immunotherapy in patients with melanoma, a highly immunogenic tumor, we performed serial PET imaging with the 1-armed CD8 antibody tracer 89ZED88082A. Methods: Immunotherapy-naïve adult patients with stage IV melanoma underwent PET scanning 2 d after receiving 10 mg of 89ZED88082A intravenously at baseline and 6-8 wk after initiation of standard-of-care immunotherapy. Tracer uptake in lesions, normal lymph nodes, and Waldeyer ring was assessed using SUVmax; other healthy tissue uptake was assessed using SUVmean Uptake in tumors and healthy lymph nodes was expressed as the geometric mean SUVmax per patient and in healthy tissue as SUVmean for all patients. Tumor response was evaluated in accordance with iRECIST version 1.1. Tumor tissue was immunohistochemically stained for CD8. Results: Serial imaging was performed for 10 of 11 enrolled patients. The geometric mean tumor SUVmax was 7.2 (95% CI, 5.6-9.4) before treatment and 7.3 (95% CI, 5.7-9.5; P = 0.89) during treatment, with spatial and temporal heterogeneity in tumor uptake. The spleen demonstrated the highest uptake among healthy tissues, and this value remained similar during treatment. After immunotherapy, 2 patients experienced a complete response, 7 a partial response, and 2 progressive disease. Changes in tumor uptake during treatment did occur but did not correlate with tumor response. Nine evaluable pretreatment tumor tissues showed a CD8-inflamed immune phenotype. Conclusion: Lesions demonstrated spatial and temporal heterogeneity in 89ZED88082A uptake within and among patients with melanoma.