Details

Autor(en) / Beteiligte

• Vilain, Ricardo E
• Menzies, Alexander M
• Wilmott, James S
• Kakavand, Hojabr
• Madore, Jason
• Guminski, Alexander
• Liniker, Elizabeth
• Kong, Benjamin Y
• Cooper, Adam J
• Howle, Julie R
• Saw, Robyn P M
• Jakrot, Valerie
• Lo, Serigne
• Thompson, John F
• Carlino, Matteo S
• Kefford, Richard F
• Long, Georgina V
• Scolyer, Richard A

Titel

Dynamic Changes in PD-L1 Expression and Immune Infiltrates Early During Treatment Predict Response to PD-1 Blockade in Melanoma

Ist Teil von

• Clinical cancer research, 2017-09, Vol.23 (17), p.5024-5033

Ort / Verlag

United States: American Association for Cancer Research Inc

Erscheinungsjahr

2017

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• Disruption of PD-L1/cytotoxic T-cell PD-1 signaling by immune checkpoint inhibitors improves survival in cancer patients. This study sought to identify changes in tumoral PD-L1 expression and tumor-associated immune cell flux with anti-PD-1 therapies in patients with melanoma, particularly early during treatment, and correlate them with treatment response. Forty-six tumor biopsies from 23 patients with unresectable AJCC stage III/IV melanoma receiving pembrolizumab/nivolumab were analyzed. Biopsies were collected prior to (PRE, = 21), within 2 months of commencing treatment (EDT, = 20) and on disease progression after previous response (PROG, = 5). Thirteen patients responded (defined as CR, PR, or durable SD by RECIST/irRC criteria), and 10 did not respond. PRE intratumoral and peritumoral PD-1 T-cell densities were sevenfold ( = 0.006) and fivefold higher ( = 0.011), respectively, in responders compared with nonresponders and correlated with degree of radiologic tumor response ( = -0.729, = 0.001 and = -0.725, = 0.001, respectively). PRE PD-L1 expression on tumor and macrophages was not significantly different between the patient groups, but tumoral PD-L1 and macrophage PD-L1 expression was higher in the EDT of responders versus nonresponders ( = 0.025 and = 0.033). Responder EDT biopsies (compared with PRE) also showed significant increases in intratumoral CD8 lymphocytes ( = 0.046) and intratumoral CD68 macrophages ( = 0.046). Higher PRE PD-1 T cells in responders suggest active suppression of an engaged immune system that is disinhibited by anti-PD-1 therapies. Furthermore, immunoprofiling of EDT biopsies for increased PD-L1 expression and immune cell infiltration showed greater predictive utility than PRE biopsies and may allow better selection of patients most likely to benefit from anti-PD-1 therapies and warrants further evaluation. .