Pan-cancer Immunogenomic Analyses Reveal Genotype-Immunophenotype Relationships and Predictors of Response to Checkpoint Blockade

Cell Reports, Journal Year: 2017, Volume and Issue: 18(1), P. 248 - 262

Published: Jan. 1, 2017

The Cancer Genome Atlas revealed the genomic landscapes of human cancers. In parallel, immunotherapy is transforming treatment advanced Unfortunately, majority patients do not respond to immunotherapy, making identification predictive markers and mechanisms resistance an area intense research. To increase our understanding tumor-immune cell interactions, we characterized intratumoral immune cancer antigenomes from 20 solid cancers created Immunome (https://tcia.at/). Cellular characterization infiltrates showed that tumor genotypes determine immunophenotypes escape mechanisms. Using machine learning, identified determinants immunogenicity developed a scoring scheme for quantification termed immunophenoscore. immunophenoscore was superior predictor response anti-cytotoxic T lymphocyte antigen-4 (CTLA-4) anti-programmed death protein 1 (anti-PD-1) antibodies in two independent validation cohorts. Our findings this resource may help inform facilitate development precision immuno-oncology.

Language: Английский

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The immune contexture in cancer prognosis and treatment

Nature Reviews Clinical Oncology, Journal Year: 2017, Volume and Issue: 14(12), P. 717 - 734

Published: July 25, 2017

Language: Английский

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Regulation and Function of the PD-L1 Checkpoint

Immunity, Journal Year: 2018, Volume and Issue: 48(3), P. 434 - 452

Published: March 1, 2018

Language: Английский

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Lung cancer

The Lancet, Journal Year: 2021, Volume and Issue: 398(10299), P. 535 - 554

Published: July 21, 2021

Language: Английский

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Tumour-intrinsic resistance to immune checkpoint blockade

Nature reviews. Immunology, Journal Year: 2019, Volume and Issue: 20(1), P. 25 - 39

Published: Sept. 30, 2019

Language: Английский

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Mechanisms of resistance to immune checkpoint inhibitors

British Journal of Cancer, Journal Year: 2018, Volume and Issue: 118(1), P. 9 - 16

Published: Jan. 1, 2018

Immune checkpoint inhibitors (ICI) targeting CTLA-4 and the PD-1/PD-L1 axis have shown unprecedented clinical activity in several types of cancer are rapidly transforming practice medical oncology. Whereas cytotoxic chemotherapy small molecule ('targeted therapies') largely act on cells directly, immune reinvigorate anti-tumour responses by disrupting co-inhibitory T-cell signalling. While resistance routinely develops patients treated with conventional therapies targeted therapies, durable suggestive long-lasting immunologic memory commonly seen large subsets ICI. However, initial response appears to be a binary event, most non-responders single-agent ICI therapy progressing at rate consistent natural history disease. In addition, late relapses now emerging longer follow-up trial populations, suggesting emergence acquired resistance. As robust biomarkers predict and/or remain elusive, mechanisms underlying innate (primary) (secondary) inferred from pre-clinical studies correlative data. Improved understanding molecular (and resistance) may not only identify novel predictive prognostic biomarkers, but also ultimately guide optimal combination/sequencing clinic. Here we review data identifying inhibition.

Language: Английский

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Immune checkpoint blockade therapy for cancer: An overview of FDA-approved immune checkpoint inhibitors

International Immunopharmacology, Journal Year: 2018, Volume and Issue: 62, P. 29 - 39

Published: July 2, 2018

Language: Английский

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Generation of Tumor-Reactive T Cells by Co-culture of Peripheral Blood Lymphocytes and Tumor Organoids

Cell, Journal Year: 2018, Volume and Issue: 174(6), P. 1586 - 1598.e12

Published: Aug. 9, 2018

Language: Английский

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Targeting autophagy in cancer

Cancer, Journal Year: 2018, Volume and Issue: 124(16), P. 3307 - 3318

Published: April 19, 2018

Autophagy is a conserved, self-degradation system that critical for maintaining cellular homeostasis during stress conditions. Dysregulated autophagy has implications in health and disease. Specifically, cancer, plays dichotomous role by inhibiting tumor initiation but supporting progression. Early results from clinical trials repurposed hydroxychloroquine cancer have suggested inhibition may be promising approach advanced cancers. In this review of the literature, authors present fundamental advances biology autophagy, approaches to targeting preclinical rationale experience with trials, potential immunity, recent developments next-generation inhibitors potential. target drug development cancer. Cancer 2018. © 2018 American Society.

Language: Английский

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Genetics and biology of prostate cancer

Genes & Development, Journal Year: 2018, Volume and Issue: 32(17-18), P. 1105 - 1140

Published: Sept. 1, 2018

Despite the high long-term survival in localized prostate cancer, metastatic cancer remains largely incurable even after intensive multimodal therapy. The lethality of advanced disease is driven by lack therapeutic regimens capable generating durable responses setting extreme tumor heterogeneity on genetic and cell biological levels. Here, we review available model systems, genome atlas, cellular functional microenvironment, tumor-intrinsic tumor-extrinsic mechanisms underlying resistance, technological advances focused detection management. These advances, along with an improved understanding adaptive to conventional therapies, anti-androgen therapy, immunotherapy, are catalyzing development more effective strategies for disease. In particular, knowledge heterotypic interactions between coevolution host cells microenvironment has illuminated novel combinations a strong potential eventual cures Improved management will also benefit from artificial intelligence-based expert decision support systems proper standard care, prognostic determinant biomarkers minimize overtreatment disease, new standards care accelerated next-generation clinical trials.

Language: Английский

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