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

Abstract

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 SUV_max; other healthy tissue uptake was assessed using SUV_mean Uptake in tumors and healthy lymph nodes was expressed as the geometric mean SUV_max per patient and in healthy tissue as SUV_mean 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 SUV_max 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.