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DOI | 10.1126/science.aao4572 ; 10.1126/science.aao4572 |
Patient HLA class I genotype influences cancer response to checkpoint blockade immunotherapy; Patient HLA class I genotype influences cancer response to checkpoint blockade immunotherapy | |
Chowell, Diego1,2; Morris, Luc G. T.2,3; Grigg, Claud M.4; Weber, Jeffrey K.5; Samstein, Robert M.1,2; Makarov, Vladimir1,2; Kuo, Fengshen1,2; Kendall, Sviatoslav M.1,2; Requena, David6; Riaz, Nadeem1,2,7; Greenbaum, Benjamin8,9,10; Carroll, James11; Garon, Edward11; Hyman, David M.12,13; Zehir, Ahmet14; Solit, David1,12,15; Berger, Michael1,14,15; Zhou, Ruhong5,16; Rizvi, Naiyer A.4; Chan, Timothy A.1,2,7,13 | |
2018-02-02 ; 2018-02-02 | |
发表期刊 | SCIENCE ; SCIENCE |
ISSN | 0036-8075 ; 0036-8075 |
EISSN | 1095-9203 ; 1095-9203 |
出版年 | 2018 ; 2018 |
卷号 | 359期号:6375页码:582-+ |
文章类型 | Article ; Article |
语种 | 英语 ; 英语 |
国家 | USA; USA |
英文摘要 | CD8(+) T cell-dependent killing of cancer cells requires efficient presentation of tumor antigens by human leukocyte antigen class I (HLA-I) molecules. However, the extent to which patient-specific HLA-I genotype influences response to anti-programmed cell death protein 1 or anti-cytotoxic T lymphocyte-associated protein 4 is currently unknown. We determined the HLA-I genotype of 1535 advanced cancer patients treated with immune checkpoint blockade (ICB). Maximal heterozygosity at HLA-I loci ("A," "B," and "C") improved overall survival after ICB compared with patients who were homozygous for at least one HLA locus. In two independent melanoma cohorts, patients with the HLA-B44 supertype had extended survival, whereas the HLA-B62 supertype (including HLA-B*15:01) or somatic loss of heterozygosity at HLA-I was associated with poor outcome. Molecular dynamics simulations of HLA-B*15:01 revealed different elements that may impair CD8(+) T cell recognition of neoantigens. Our results have important implications for predicting response to ICB and for the design of neoantigen-based therapeutic vaccines. ; CD8(+) T cell-dependent killing of cancer cells requires efficient presentation of tumor antigens by human leukocyte antigen class I (HLA-I) molecules. However, the extent to which patient-specific HLA-I genotype influences response to anti-programmed cell death protein 1 or anti-cytotoxic T lymphocyte-associated protein 4 is currently unknown. We determined the HLA-I genotype of 1535 advanced cancer patients treated with immune checkpoint blockade (ICB). Maximal heterozygosity at HLA-I loci ("A," "B," and "C") improved overall survival after ICB compared with patients who were homozygous for at least one HLA locus. In two independent melanoma cohorts, patients with the HLA-B44 supertype had extended survival, whereas the HLA-B62 supertype (including HLA-B*15:01) or somatic loss of heterozygosity at HLA-I was associated with poor outcome. Molecular dynamics simulations of HLA-B*15:01 revealed different elements that may impair CD8(+) T cell recognition of neoantigens. Our results have important implications for predicting response to ICB and for the design of neoantigen-based therapeutic vaccines. |
领域 | 地球科学 ; 地球科学 ; 气候变化 ; 气候变化 ; 资源环境 ; 资源环境 |
收录类别 | SCI-E ; SCI-E |
WOS记录号 | WOS:000423795800044 ; WOS:000423795800044 |
WOS关键词 | PD-1 BLOCKADE ; PD-1 BLOCKADE ; HISTOCOMPATIBILITY ANTIGENS ; HISTOCOMPATIBILITY ANTIGENS ; MUTATIONAL LANDSCAPE ; MUTATIONAL LANDSCAPE ; METASTATIC MELANOMA ; METASTATIC MELANOMA ; CTLA-4 BLOCKADE ; CTLA-4 BLOCKADE ; RESISTANCE ; RESISTANCE ; THERAPY ; THERAPY ; MOLECULES ; MOLECULES ; HIV-1 ; HIV-1 ; IDENTIFICATION ; IDENTIFICATION |
WOS类目 | Multidisciplinary Sciences ; Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics ; Science & Technology - Other Topics |
URL | 查看原文 |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/197896 |
专题 | 地球科学 资源环境科学 气候变化 |
作者单位 | 1.Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, New York, NY 10065 USA; 2.Mem Sloan Kettering Canc Ctr, Immunogen & Precis Oncol Platform, New York, NY 10065 USA; 3.Mem Sloan Kettering Canc Ctr, Dept Surg, New York, NY 10065 USA; 4.NewYork Presbyterian Columbia Univ, Med Ctr, 177 Ft Washington Ave, New York, NY 10032 USA; 5.IBM Thomas J Watson Res Ctr, Yorktown Hts, NY 10598 USA; 6.Rockefeller Univ, Lab Cellular Biophys, New York, NY 10065 USA; 7.Mem Sloan Kettering Canc Ctr, Dept Radiat Oncol, New York, NY 10065 USA; 8.Icahn Sch Med Mt Sinai, Tisch Canc Inst, Dept Med, New York, NY 10029 USA; 9.Icahn Sch Med Mt Sinai, Tisch Canc Inst, Dept Oncol Sci, New York, NY 10029 USA; 10.Icahn Sch Med Mt Sinai, Tisch Canc Inst, Dept Pathol, New York, NY 10029 USA; 11.Univ Calif Los Angeles, David Geffen Sch Med, 2825 Santa Monica Blvd,Suite 200, Santa Monica, CA 90404 USA; 12.Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10065 USA; 13.Weill Cornell Sch Med, New York, NY 10065 USA; 14.Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10065 USA; 15.Mem Sloan Kettering Canc Ctr, Marie Josee & Henry R Kravis Ctr Mol Oncol, New York, NY 10065 USA; 16.Columbia Univ, Dept Chem, New York, NY 10027 USA |
推荐引用方式 GB/T 7714 | Chowell, Diego,Morris, Luc G. T.,Grigg, Claud M.,et al. Patient HLA class I genotype influences cancer response to checkpoint blockade immunotherapy, Patient HLA class I genotype influences cancer response to checkpoint blockade immunotherapy[J]. SCIENCE, SCIENCE,2018, 2018,359, 359(6375):582-+, 582-+. |
APA | Chowell, Diego.,Morris, Luc G. T..,Grigg, Claud M..,Weber, Jeffrey K..,Samstein, Robert M..,...&Chan, Timothy A..(2018).Patient HLA class I genotype influences cancer response to checkpoint blockade immunotherapy.SCIENCE,359(6375),582-+. |
MLA | Chowell, Diego,et al."Patient HLA class I genotype influences cancer response to checkpoint blockade immunotherapy".SCIENCE 359.6375(2018):582-+. |
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