Details

Autor(en) / Beteiligte

• Le, Dung T
• Uram, Jennifer N
• Wang, Hao
• Bartlett, Bjarne R
• Kemberling, Holly
• Eyring, Aleksandra D
• Skora, Andrew D
• Luber, Brandon S
• Azad, Nilofer S
• Laheru, Dan
• Biedrzycki, Barbara
• Donehower, Ross C
• Zaheer, Atif
• Fisher, George A
• Crocenzi, Todd S
• Lee, James J
• Duffy, Steven M
• Goldberg, Richard M
• de la Chapelle, Albert
• Koshiji, Minori
• Bhaijee, Feriyl
• Huebner, Thomas
• Hruban, Ralph H
• Wood, Laura D
• Cuka, Nathan
• Pardoll, Drew M
• Papadopoulos, Nickolas
• Kinzler, Kenneth W
• Zhou, Shibin
• Cornish, Toby C
• Taube, Janis M
• Anders, Robert A
• Eshleman, James R
• Vogelstein, Bert
• Diaz, Luis A

Titel

PD-1 Blockade in Tumors with Mismatch-Repair Deficiency

Ist Teil von

• The New England journal of medicine, 2015-06, Vol.372 (26), p.2509-2520

Ort / Verlag

United States: Massachusetts Medical Society

Erscheinungsjahr

2015

Quelle

MEDLINE

Beschreibungen/Notizen

• Persons with mismatch repair–deficient tumors are more likely than persons with mismatch repair–proficient tumors to benefit from pembrolizumab — which augments T-cell effector function — probably because mismatch repair–deficient tumors express many more neoantigens. The programmed death 1 (PD-1) pathway is a negative feedback system that represses Th1 cytotoxic immune responses and that, if unregulated, can damage the host. 1 – 3 It is up-regulated in many tumors and in their surrounding microenvironment. Blockade of this pathway with antibodies to PD-1 or its ligands has led to remarkable clinical responses in patients with many different types of cancer, including melanomas, non–small-cell lung cancer, renal-cell carcinoma, bladder cancer, and Hodgkin’s lymphoma. 4 – 10 The expression of PD-1 ligands (PD-L1 or PD-L2) on the surface of tumor cells or immune cells is an important — but not a definitive . . .