Epigenetic modulation of antitumor immunity for improved cancer immunotherapy DOI Creative Commons
Enyong Dai, Zhi Zhu,

Shudipto Wahed

et al.

Molecular Cancer, Journal Year: 2021, Volume and Issue: 20(1)

Published: Dec. 20, 2021

Abstract Epigenetic mechanisms play vital roles not only in cancer initiation and progression, but also the activation, differentiation effector function(s) of immune cells. In this review, we summarize current literature related to epigenomic dynamics cells impacting cell fate functionality, immunogenicity Some important immune-associated genes, such as granzyme B, IFN-γ, IL-2, IL-12, FoxP3 STING, are regulated via epigenetic or/and cells, checkpoint molecules (PD-1, CTLA-4, TIM-3, LAG-3, TIGIT) expressed by tumor-associated stromal Thus, therapeutic strategies implementing modulating drugs expected significantly impact tumor microenvironment (TME) promoting transcriptional metabolic reprogramming local populations, resulting inhibition immunosuppressive (MDSCs Treg) activation anti-tumor T professional antigen presenting (APC), well which can serve non-professional APC. latter instance, agents may coordinately promote inducing de novo expression transcriptionally repressed antigens, increasing neoantigens MHC processing/presentation machinery, activating immunogenic death (ICD). ICD provides a rich source immunogens for cross-priming sensitizing interventional immunotherapy. way, modulators be envisioned effective components combination immunotherapy approaches capable mediating superior efficacy.

Language: Английский

Hybrid cellular membrane nanovesicles amplify macrophage immune responses against cancer recurrence and metastasis DOI Creative Commons
Lang Rao, Lei Wu, Zhida Liu

et al.

Nature Communications, Journal Year: 2020, Volume and Issue: 11(1)

Published: Sept. 30, 2020

Abstract Effectively activating macrophages against cancer is promising but challenging. In particular, cells express CD47, a ‘don’t eat me’ signal that interacts with regulatory protein alpha (SIRPα) on to prevent phagocytosis. Also, secrete stimulating factors, which polarize tumor-associated from an antitumor M1 phenotype tumorigenic M2 phenotype. Here, we report hybrid cell membrane nanovesicles (known as hNVs) displaying SIRPα variants significantly increased affinity CD47 and containing M2-to-M1 repolarization signals can disable both mechanisms. The hNVs block CD47-SIRPα signaling axis while promoting within tumor microenvironment, preventing local recurrence distant metastasis in malignant melanoma models. Furthermore, by loading stimulator of interferon genes (STING) agonist, lead potent inhibition poorly immunogenic triple negative breast model. are safe, stable, drug loadable, suitable for genetic editing. These properties, combined the capabilities inherited source cells, make attractive immunotherapy.

Language: Английский

Citations

293
Mitochondrial DNA drives abscopal responses to radiation that are inhibited by autophagy DOI
Takahiro Yamazaki, Alexander Kirchmair, Ai Sato

et al.

Nature Immunology, Journal Year: 2020, Volume and Issue: 21(10), P. 1160 - 1171

Published: Aug. 3, 2020

Language: Английский

Citations

286
Tumor mutational burden quantification from targeted gene panels: major advancements and challenges DOI Creative Commons
Laura Fancello, Sara Gandini, Pier Giuseppe Pelicci

et al.

Journal for ImmunoTherapy of Cancer, Journal Year: 2019, Volume and Issue: 7(1)

Published: July 15, 2019

Tumor mutational burden (TMB), the total number of somatic coding mutations in a tumor, is emerging as promising biomarker for immunotherapy response cancer patients. TMB can be quantitated by NGS-based sequencing technologies. Whole Exome Sequencing (WES) allows comprehensive measurement and considered gold standard. However, to date WES remains confined research settings, due high cost large genomic space sequenced. In clinical setting, instead, targeted enrichment panels (gene panels) various sizes are routine technology assessment. This stimulated development methods panel-based quantification, prompted multiplication studies assessing whether confidently estimated from smaller sampled gene panels. this review, we inventory collection available tested purpose, illustrating their technical specifications describing accuracy value Moreover, highlight how experimental, platform-related or methodological variables, well bioinformatic pipelines, influence quantification. The lack harmonization adequate convert estimates across different robust predictive cutoffs, currently represents one main limitations adopt practice. overview on heterogeneous landscape quantification aims at providing context discuss common standards illustrates strong need further validation consolidation interpretation values.

Language: Английский

Citations

283
Calreticulin and cancer DOI Open Access
Jitka Fučíková,

Radek Špíšek,

Guido Kroemer

et al.

Cell Research, Journal Year: 2020, Volume and Issue: 31(1), P. 5 - 16

Published: July 30, 2020

Language: Английский

Citations

283
Acetylation-dependent regulation of PD-L1 nuclear translocation dictates the efficacy of anti-PD-1 immunotherapy DOI
Yang Gao, Naoe Taira Nihira, Xia Bu

et al.

Nature Cell Biology, Journal Year: 2020, Volume and Issue: 22(9), P. 1064 - 1075

Published: Aug. 24, 2020

Language: Английский

Citations

277
Epigenetic silencing by SETDB1 suppresses tumour intrinsic immunogenicity DOI
Gabriel K. Griffin, Jingyi Wu, Arvin Iracheta‐Vellve

et al.

Nature, Journal Year: 2021, Volume and Issue: 595(7866), P. 309 - 314

Published: May 5, 2021

Language: Английский

Citations

267
Immunity, Hypoxia, and Metabolism–the Ménage à Trois of Cancer: Implications for Immunotherapy DOI Open Access
Carla Riera‐Domingo, Annette Audigé, Sara Granja

et al.

Physiological Reviews, Journal Year: 2019, Volume and Issue: 100(1), P. 1 - 102

Published: Aug. 15, 2019

It is generally accepted that metabolism able to shape the immune response. Only recently we are gaining awareness metabolic crosstalk between different tumor compartments strongly contributes harsh microenvironment (TME) and ultimately impairs cell fitness effector functions. The major aims of this review provide an overview on system in cancer; position oxygen shortage competition as ground a restrictive TME important players anti-tumor response; define how immunotherapies affect hypoxia/oxygen delivery landscape tumor; vice versa, metabolites within impinge success immunotherapies. By analyzing preclinical clinical endeavors, will discuss characterization can identify novel targets signatures could be exploited combination with standard help predict benefit new traditional immunotherapeutic drugs.

Language: Английский

Citations

252
Understanding the tumor microenvironment for effective immunotherapy DOI Creative Commons

Habib Sadeghi Rad,

James Monkman, Majid Ebrahimi Warkiani

et al.

Medicinal Research Reviews, Journal Year: 2020, Volume and Issue: 41(3), P. 1474 - 1498

Published: Dec. 4, 2020

Abstract Advances in immunotherapy have led to durable and long‐term benefits a subset of patients across number solid tumor types. Understanding the subsets that respond immune checkpoint inhibitors at cellular level, context their microenvironment (TME) is becoming increasingly important. The TME composed heterogeneous milieu cells. landscape can inhibit or promote initiation progression; thus, deeper understanding immunity necessary develop immunotherapeutic strategies. Recent developments focused on characterizing contexture (type, density, function) discover mechanisms biomarkers may predict treatment outcomes. This has, part, been powered by advancements spatial characterization technologies. In this review article, we address role specific cells within various stages progression how determinants affecting growth are used therapeutically.

Language: Английский

Citations

239
Trial watch: STING agonists in cancer therapy DOI Creative Commons
Julie Le Naour, Laurence Zitvogel, Lorenzo Galluzzi

et al.

OncoImmunology, Journal Year: 2020, Volume and Issue: 9(1)

Published: Jan. 1, 2020

Stimulator of interferon response cGAMP interactor 1 (STING1, best known as STING) is an endoplasmic reticulum-sessile protein that serves a signaling hub, receiving input from several pattern recognition receptors, most which sense ectopic DNA species in the cytosol. In particular, STING ensures production type I (IFN) to invading viruses, bacterial pathogens, well leaking mitochondria or nucleus (e.g., cells exposed chemotherapy radiotherapy). As IFN critical for initiation anticancer immune responses, pharmaceutical industry has generated molecules directly activate use oncological indications. Such agonists are being tested clinical trials with rationale activating tumor tumor-infiltrating (including dendritic cells) elicit immunostimulatory effects, alone combination range established chemotherapeutic and immunotherapeutic regimens. this Trial Watch, we discuss preclinical evidence accumulating experience shaping design Phase II evaluate safety preliminary efficacy cancer patients.

Language: Английский

Citations

227
Trial watch: TLR3 agonists in cancer therapy DOI Creative Commons
Julie Le Naour, Lorenzo Galluzzi, Laurence Zitvogel

et al.

OncoImmunology, Journal Year: 2020, Volume and Issue: 9(1)

Published: Jan. 1, 2020

Toll-like receptor 3 (TLR3) is a pattern recognition that senses exogenous (viral) as well endogenous (mammalian) double-stranded RNA in endosomes. On activation, TLR3 initiates signal transduction pathway culminates with the secretion of pro-inflammatory cytokines including type I interferon (IFN). The latter essential not only for innate immune responses to infection but also initiation antigen-specific immunity against viruses and malignant cells. These aspects biology have supported development various agonists use stand-alone agents or combined other therapeutic modalities cancer patients. Here, we review recent preclinical clinical advances oncological disorders.Abbreviations cDC, conventional dendritic cell; CMT, cytokine modulating treatment; CRC, colorectal carcinoma; CTL, cytotoxic T lymphocyte; DC, dsRNA, RNA; FLT3LG, fms-related tyrosine kinase ligand; HNSCC, head neck squamous cell IFN, interferon; IL, interleukin; ISV, situ vaccine; MUC1, mucin 1, surface associated; PD-1, programmed death 1; PD-L1, death-ligand polyA:U, polyadenylic:polyuridylic acid; polyI:C, polyriboinosinic:polyribocytidylic TLR,

Language: Английский

Citations

225