Intratumoral immune cell infiltrates, FoxP3, and indoleamine 2,3-dioxygenase in patients with melanoma undergoing CTLA4 blockade.

摘要: Purpose: CTL-associated antigen 4 (CTLA4)-blocking monoclonal antibodies induce long-term regression of metastatic melanoma in some patients, but the exact mechanism is unknown. In this study, biopsies selected accessible tumor lesions from patients treated with tremelimumab were examined to further elucidate its antitumor activity. Experimental Design: Fifteen 7 who had been (CP-675,206) collected. Samples analyzed for markers, immune cell subset presence T regulatory-specific transcription factor FoxP3 and immunosuppressive enzyme indoleamine 2,3-dioxygenase (IDO). Results: Clinically responding diffuse intratumoral infiltrates CD8 + cells that markedly increased cases where comparison a baseline biopsy was available. Nonregressing sparse, patchy infiltrates. Patients regressing an frequency or without concomitant increase CD4 cells. Two 3 paired samples showed slight number postdosing biopsies. samples, intensity IDO staining macrophages and/or no clear pattern change postdosing. Conclusions: Administration associated massive CTLs tumors varying effects on expression IDO.