دورية أكاديمية
Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade.
| العنوان: | Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade. |
|---|---|
| المؤلفون: | Le, Dung T, Durham, Jennifer N, Smith, Kellie N, Wang, Hao, Bartlett, Bjarne R, Aulakh, Laveet K, Lu, Steve, Kemberling, Holly, Wilt, Cara, Luber, Brandon S, Wong, Fay, Azad, Nilofer S, Rucki, Agnieszka A, Laheru, Dan, Donehower, Ross, Zaheer, Atif, Fisher, George A, Crocenzi, Todd S, Lee, James J, Greten, Tim F, Duffy, Austin G, Ciombor, Kristen K, Eyring, Aleksandra D, Lam, Bao H, Joe, Andrew, Kang, S Peter, Holdhoff, Matthias, Danilova, Ludmila, Cope, Leslie, Meyer, Christian, Zhou, Shibin, Goldberg, Richard M, Armstrong, Deborah K, Bever, Katherine M, Fader, Amanda N, Taube, Janis, Housseau, Franck, Spetzler, David, Xiao, Nianqing, Pardoll, Drew M, Papadopoulos, Nickolas, Kinzler, Kenneth W, Eshleman, James R, Vogelstein, Bert, Anders, Robert A, Diaz, Luis A |
| المصدر: | Articles, Abstracts, and Reports |
| بيانات النشر: | Providence St. Joseph Health Digital Commons |
| سنة النشر: | 2017 |
| المجموعة: | Providence St. Joseph Health Digital Commons |
| مصطلحات موضوعية: | Adult, Aged, 80 and over, Antibodies, Monoclonal, Humanized, Antigens, Neoplasm, Biomarkers, Tumor, Brain Neoplasms, Cell Cycle Checkpoints, Colorectal Neoplasms, DNA Mismatch Repair, Disease-Free Survival, Female, Humans, Male, Middle Aged, Mutation, Neoplastic Syndromes, Hereditary, Programmed Cell Death 1 Receptor, T-Lymphocytes, Young Adult, Oncology |
| الوصف: | The genomes of cancers deficient in mismatch repair contain exceptionally high numbers of somatic mutations. In a proof-of-concept study, we previously showed that colorectal cancers with mismatch repair deficiency were sensitive to immune checkpoint blockade with antibodies to programmed death receptor-1 (PD-1). We have now expanded this study to evaluate the efficacy of PD-1 blockade in patients with advanced mismatch repair-deficient cancers across 12 different tumor types. Objective radiographic responses were observed in 53% of patients, and complete responses were achieved in 21% of patients. Responses were durable, with median progression-free survival and overall survival still not reached. Functional analysis in a responding patient demonstrated rapid in vivo expansion of neoantigen-specific T cell clones that were reactive to mutant neopeptides found in the tumor. These data support the hypothesis that the large proportion of mutant neoantigens in mismatch repair-deficient cancers make them sensitive to immune checkpoint blockade, regardless of the cancers' tissue of origin. |
| نوع الوثيقة: | text |
| وصف الملف: | application/pdf |
| اللغة: | unknown |
| العلاقة: | https://digitalcommons.psjhealth.org/publications/1341Test; https://digitalcommons.psjhealth.org/cgi/viewcontent.cgi?article=2333&context=publicationsTest |
| الإتاحة: | https://digitalcommons.psjhealth.org/publications/1341Test https://digitalcommons.psjhealth.org/cgi/viewcontent.cgi?article=2333&context=publicationsTest |
| رقم الانضمام: | edsbas.334A53A1 |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |