Tumor neoantigens: from basic research to clinical applications DOI Creative Commons
Tao Jiang, Tao Shi, Henghui Zhang

et al.

Journal of Hematology & Oncology, Journal Year: 2019, Volume and Issue: 12(1)

Published: Sept. 6, 2019

Tumor neoantigen is the truly foreign protein and entirely absent from normal human organs/tissues. It could be specifically recognized by neoantigen-specific T cell receptors (TCRs) in context of major histocompatibility complexes (MHCs) molecules. Emerging evidence has suggested that neoantigens play a critical role tumor-specific cell-mediated antitumor immune response successful cancer immunotherapies. From theoretical perspective, an ideal immunotherapy target because they are distinguished germline as non-self host system. Neoantigen-based therapeutic personalized vaccines adoptive transfer have shown promising preliminary results. Furthermore, recent studies significant escape, immunoediting, sensitivity to checkpoint inhibitors. In this review, we systematically summarize advances understanding identification its on current We also discuss ongoing development strategies based future clinical applications.

Language: Английский

Roles of the immune system in cancer: from tumor initiation to metastatic progression DOI Open Access
Hugo González, Catharina Hagerling, Zena Werb

et al.

Genes & Development, Journal Year: 2018, Volume and Issue: 32(19-20), P. 1267 - 1284

Published: Oct. 1, 2018

The presence of inflammatory immune cells in human tumors raises a fundamental question oncology: How do cancer avoid the destruction by attack? In principle, tumor development can be controlled cytotoxic innate and adaptive cells; however, as develops from neoplastic tissue to clinically detectable tumors, evolve different mechanisms that mimic peripheral tolerance order tumoricidal attack. Here, we provide an update recent accomplishments, unifying concepts, future challenges study tumor-associated cells, with emphasis on metastatic carcinomas.

Language: Английский

Citations

1794

CD8+ cytotoxic T lymphocytes in cancer immunotherapy: A review DOI
Bagher Farhood, Masoud Najafi, Keywan Mortezaee

et al.

Journal of Cellular Physiology, Journal Year: 2018, Volume and Issue: 234(6), P. 8509 - 8521

Published: Nov. 22, 2018

CD8+ cytotoxic T lymphocytes (CTLs) are preferred immune cells for targeting cancer. During cancer progression, CTLs encounter dysfunction and exhaustion due to immunerelated tolerance immunosuppression within the tumor microenvironment (TME), with all favor adaptive immune-resistance. Cancer-associated fibroblasts (CAFs), macrophage type 2 (M2) cells, regulatory (Tregs) could make immunologic barriers against CD8 + cell-mediated antitumor responses. Thus, needed be primed activated toward effector in a process called immunity cycle making durable efficient The cell priming is directed essentially as corroboration work between of innate including dendritic (DCs) natural killer (NK) CD4 adoptive immunity. Upon activation, infiltrate core or invading site (so-called infiltrated-inflamed [I-I] TME) take essential roles killing cells. Exogenous reactivation and/or can possible using rational immunotherapy strategies. increase ratio costimulatory coinhibitory mediators checkpoint blockade (ICB) approach. Programmed death-1 receptor (PD-1)-ligand (PD-L1) CTL-associated antigen 4 (CTLA-4) receptors that targeted relieving renewing their priming, respectively, thereby eliminating antigen-expressing Due diverse relation Tregs, Treg activity dampened increasing number rescuing functional potential induce immunosensitivity

Language: Английский

Citations

1337

Tumor targeting via EPR: Strategies to enhance patient responses DOI

Susanne K. Golombek,

Jan‐Niklas May, Benjamin Theek

et al.

Advanced Drug Delivery Reviews, Journal Year: 2018, Volume and Issue: 130, P. 17 - 38

Published: May 1, 2018

Language: Английский

Citations

1065

Combination strategies with PD-1/PD-L1 blockade: current advances and future directions DOI Creative Commons
Ming Yi, Xiaoli Zheng,

Mengke Niu

et al.

Molecular Cancer, Journal Year: 2022, Volume and Issue: 21(1)

Published: Jan. 21, 2022

Antibodies targeting programmed cell death protein-1 (PD-1) or its ligand PD-L1 rescue T cells from exhausted status and revive immune response against cancer cells. Based on the immense success in clinical trials, ten α-PD-1 (nivolumab, pembrolizumab, cemiplimab, sintilimab, camrelizumab, toripalimab, tislelizumab, zimberelimab, prolgolimab, dostarlimab) three α-PD-L1 antibodies (atezolizumab, durvalumab, avelumab) have been approved for various types of cancers. Nevertheless, low rate α-PD-1/PD-L1 therapy remains to be resolved. For most patients, PD-1/PD-L1 pathway is not sole speed-limiting factor antitumor immunity, it insufficient motivate effective by blocking axis. It has validated that some combination therapies, including plus chemotherapy, radiotherapy, angiogenesis inhibitors, targeted therapy, other checkpoint agonists co-stimulatory molecule, stimulator interferon genes agonists, fecal microbiota transplantation, epigenetic modulators, metabolic superior efficacies higher rates. Moreover, bifunctional bispecific containing moiety also elicited more potent activity. These strategies simultaneously boost multiple processes cancer-immunity cycle, remove immunosuppressive brakes, orchestrate an immunosupportive tumor microenvironment. In this review, we summarized synergistic mechanisms with therapies. focused advances α-PD-1/PD-L1-based immunomodulatory studies. Given heterogeneity across patients types, individualized selection could improve effects relieve treatment resistance.

Language: Английский

Citations

909

Cyclin D–CDK4 kinase destabilizes PD-L1 via cullin 3–SPOP to control cancer immune surveillance DOI
Jinfang Zhang, Xia Bu, Haizhen Wang

et al.

Nature, Journal Year: 2017, Volume and Issue: 553(7686), P. 91 - 95

Published: Nov. 16, 2017

Language: Английский

Citations

838

Phagocytosis checkpoints as new targets for cancer immunotherapy DOI
Mingye Feng, Wen Jiang, Betty Y.S. Kim

et al.

Nature reviews. Cancer, Journal Year: 2019, Volume and Issue: 19(10), P. 568 - 586

Published: Aug. 28, 2019

Language: Английский

Citations

765

SynergyFinder 2.0: visual analytics of multi-drug combination synergies DOI Creative Commons
Aleksandr Ianevski,

Anil K. Giri,

Tero Aittokallio

et al.

Nucleic Acids Research, Journal Year: 2020, Volume and Issue: 48(W1), P. W488 - W493

Published: March 25, 2020

Abstract SynergyFinder (https://synergyfinder.fimm.fi) is a stand-alone web-application for interactive analysis and visualization of drug combination screening data. Since its first release in 2017, has become widely used web-tool both the discovery novel synergistic combinations pre-clinical model systems (e.g. cell lines or primary patient-derived cells), better understanding mechanisms treatment efficacy resistance. Here, we describe latest version (release 2.0), which extensively been upgraded through addition features supporting especially higher-order data analytics exploratory multi-drug synergy patterns, along with automated outlier detection procedure, extended curve-fitting functionality statistical replicate measurements. A number additional improvements were also implemented based on user requests, including new export options, updated interface, as well enhanced stability performance web-tool. With these improvements, 2.0 expected to greatly extend potential applications various areas combinatorial precision medicine.

Language: Английский

Citations

749

Targeting inflammation in atherosclerosis — from experimental insights to the clinic DOI Open Access
Oliver Soehnlein, Peter Libby

Nature Reviews Drug Discovery, Journal Year: 2021, Volume and Issue: 20(8), P. 589 - 610

Published: May 11, 2021

Language: Английский

Citations

746

Employment of enhanced permeability and retention effect (EPR): Nanoparticle-based precision tools for targeting of therapeutic and diagnostic agent in cancer DOI

Dnyaneshwar Kalyane,

Nidhi Raval,

Rahul Maheshwari

et al.

Materials Science and Engineering C, Journal Year: 2019, Volume and Issue: 98, P. 1252 - 1276

Published: Jan. 18, 2019

Language: Английский

Citations

725

Control of Metastasis by NK Cells DOI Creative Commons
Alejandro López‐Soto, Segundo González, Mark J. Smyth

et al.

Cancer Cell, Journal Year: 2017, Volume and Issue: 32(2), P. 135 - 154

Published: Aug. 1, 2017

Language: Английский

Citations

654