Cell, Journal Year: 2020, Volume and Issue: 183(3), P. 818 - 834.e13
Published: Oct. 1, 2020
Language: Английский
Science, Journal Year: 2018, Volume and Issue: 359(6382), P. 1350 - 1355
Published: March 22, 2018
The release of negative regulators immune activation (immune checkpoints) that limit antitumor responses has resulted in unprecedented rates long-lasting tumor patients with a variety cancers. This can be achieved by antibodies blocking the cytotoxic T lymphocyte–associated protein 4 (CTLA-4) or programmed cell death 1 (PD-1) pathway, either alone combination. main premise for inducing an response is preexistence cells were limited specific checkpoints. Most who have maintain disease control, yet one-third relapse. Mechanisms acquired resistance are currently poorly understood, but evidence points to alterations converge on antigen presentation and interferon-γ signaling pathways. New-generation combinatorial therapies may overcome mechanisms checkpoint therapy.
Language: Английский
Citations
5362
Nature Reviews Drug Discovery, Journal Year: 2019, Volume and Issue: 18(3), P. 197 - 218
Published: Jan. 4, 2019
Language: Английский
Citations
2639
Nature reviews. Cancer, Journal Year: 2019, Volume and Issue: 19(3), P. 133 - 150
Published: Feb. 12, 2019
Language: Английский
Citations
1962
Science, Journal Year: 2018, Volume and Issue: 362(6411)
Published: Oct. 11, 2018
Programmed cell death protein-1 (PD-1) and programmed ligand-1 (PD-L1) checkpoint blockade immunotherapy elicits durable antitumor effects in multiple cancers, yet not all patients respond. We report the evaluation of >300 patient samples across 22 tumor types from four KEYNOTE clinical trials. Tumor mutational burden (TMB) a T cell-inflamed gene expression profile (GEP) exhibited joint predictive utility identifying responders nonresponders to PD-1 antibody pembrolizumab. TMB GEP were independently response demonstrated low correlation, suggesting that they capture distinct features neoantigenicity activation. Analysis The Cancer Genome Atlas database showed have analysis by stratification revealed biomarker-defined patterns targetable-resistance biology. These biomarkers may trial design guiding rational selection anti-PD-1 monotherapy combination regimens.
Language: Английский
Citations
1954
Nature Reviews Clinical Oncology, Journal Year: 2018, Volume and Issue: 16(3), P. 151 - 167
Published: Dec. 6, 2018
Language: Английский
Citations
1433
Cell, Journal Year: 2021, Volume and Issue: 184(21), P. 5309 - 5337
Published: Oct. 1, 2021
Language: Английский
Citations
1083
Nature Reviews Gastroenterology & Hepatology, Journal Year: 2021, Volume and Issue: 18(8), P. 525 - 543
Published: April 13, 2021
Hepatocellular carcinoma (HCC) is a prevalent disease with progression that modulated by the immune system. Systemic therapy used in advanced stage and until 2017 consisted only of antiangiogenic tyrosine kinase inhibitors (TKIs). Immunotherapy checkpoint has shown strong anti-tumour activity subset patients combination anti-PDL1 antibody atezolizumab VEGF-neutralizing bevacizumab or will soon become standard care as first-line for HCC, whereas anti-PD1 agents nivolumab pembrolizumab are after TKIs several regions. Other strategies such adoptive T-cell transfer, vaccination virotherapy have not yet demonstrated consistent clinical activity. Major unmet challenges HCC immunotherapy discovery validation predictive biomarkers, advancing treatment to earlier stages disease, applying liver dysfunction more effective combinatorial sequential approaches. Combinations other systemic local treatments perceived most promising opportunities some already under evaluation large-scale trials. This Review provides up-to-date information on best use currently available immunotherapies therapeutic development. Immunotherapeutic interventions might be tools hepatocellular carcinoma. carcinoma, mechanisms response resistance,
Language: Английский
Citations
947
Cancer Cell, Journal Year: 2018, Volume and Issue: 33(5), P. 843 - 852.e4
Published: April 12, 2018
Combination immune checkpoint blockade has demonstrated promising benefit in lung cancer, but predictors of response to combination therapy are unknown. Using whole-exome sequencing examine non-small-cell cancer (NSCLC) treated with PD-1 plus CTLA-4 blockade, we found that high tumor mutation burden (TMB) predicted improved objective response, durable benefit, and progression-free survival. TMB was independent PD-L1 expression the strongest feature associated efficacy multivariable analysis. The low rate NSCLCs demonstrates immunotherapy does not overcome negative predictive impact TMB. This study association between NSCLC. should be incorporated future trials examining PD-(L)1
Language: Английский
Citations
941
Science, Journal Year: 2018, Volume and Issue: 359(6382), P. 1355 - 1360
Published: March 22, 2018
Cancer is characterized by an accumulation of genetic alterations. Somatic mutations can generate cancer-specific neoepitopes that are recognized autologous T cells as foreign and constitute ideal cancer vaccine targets. Every tumor has its own unique composition mutations, with only a small fraction shared between patients. Technological advances in genomics, data science, immunotherapy now enable the rapid mapping within genome, rational selection targets, on-demand production therapy customized to patient’s individual tumor. First-in-human clinical trials personalized vaccines have shown feasibility, safety, immunotherapeutic activity targeting mutation signatures. With vaccination development being promoted emerging innovations digital age, vaccinating patient may become first truly treatment for cancer.
Language: Английский
Citations
924
Cancer Cell, Journal Year: 2021, Volume and Issue: 39(6), P. 845 - 865.e7
Published: May 20, 2021
Language: Английский
Citations
830