The P2X7 receptor modulates immune cells infiltration, ectonucleotidases expression and extracellular ATP levels in the tumor microenvironment DOI Creative Commons
Elena De Marchi, Elisa Orioli, Anna Pegoraro

et al.

Oncogene, Journal Year: 2019, Volume and Issue: 38(19), P. 3636 - 3650

Published: Jan. 17, 2019

In the tumor microenvironment (TME) ATP and its receptor P2X7 exert a pivotal influence on cancer growth tumor–host interactions. Here we analyzed different effect of genetic deficiency versus antagonism response against P2X7-expressing implanted tumors. We focused immune cell expression degrading enzymes CD39 CD73 in vivo measured TME's ATP. The infiltrate tumors growing null mice shows decrease CD8+ cells an increased number Tregs, overexpressing fitness markers OX40, PD-1, CD73. A similar Treg phenotype is also present spleen tumor-bearing it paralleled by proinflammatory cytokines increase TGF-β. Differently, systemic administration blocker A740003 wild-type left unaltered tumor-infiltrating lymphocytes but CD4+ effector decreased their blockade did not affect composition or ectonucleotidase circulating INF-γ. Augmented was mirrored TME concentration nucleotide reduced secretion from cells. On contrary, levels remained upon antagonism, owing to release cancerous diminished dendritic These data point at as key determinant due combined action infiltrate, ectonucleotidases, release.

Language: Английский

Immunostimulation with chemotherapy in the era of immune checkpoint inhibitors DOI
Lorenzo Galluzzi, Juliette Humeau,

Aitziber Buqué

et al.

Nature Reviews Clinical Oncology, Journal Year: 2020, Volume and Issue: 17(12), P. 725 - 741

Published: Aug. 5, 2020

Language: Английский

Citations

1035
Drug resistance and combating drug resistance in cancer DOI Open Access
Xuan Wang, Haiyun Zhang, Xiaozhuo Chen

et al.

Cancer Drug Resistance, Journal Year: 2019, Volume and Issue: unknown

Published: Jan. 1, 2019

Cancer Drug Resistance is an open access journal, focusing on pharmacological aspects of drug resistance and its reversal, molecular mechanisms classes, etc. Both clinical experimental in cancer are included.

Language: Английский

Citations

902
Consensus guidelines for the definition, detection and interpretation of immunogenic cell death DOI Creative Commons
Lorenzo Galluzzi, Ilio Vitale, Sarah H. Warren

et al.

Journal for ImmunoTherapy of Cancer, Journal Year: 2020, Volume and Issue: 8(1), P. e000337 - e000337

Published: March 1, 2020

Cells succumbing to stress via regulated cell death (RCD) can initiate an adaptive immune response associated with immunological memory, provided they display sufficient antigenicity and adjuvanticity. Moreover, multiple intracellular microenvironmental features determine the propensity of RCD drive immunity. Here, we provide updated operational definition immunogenic (ICD), discuss key factors that dictate ability dying cells response, summarize experimental assays are currently available for assessment ICD in vitro vivo, formulate guidelines their interpretation.

Language: Английский

Citations

861
Detection of immunogenic cell death and its relevance for cancer therapy DOI Creative Commons
Jitka Fučíková, Oliver Kepp, Lenka Kašíková

et al.

Cell Death and Disease, Journal Year: 2020, Volume and Issue: 11(11)

Published: Nov. 26, 2020

Abstract Chemotherapy, radiation therapy, as well targeted anticancer agents can induce clinically relevant tumor-targeting immune responses, which critically rely on the antigenicity of malignant cells and their capacity to generate adjuvant signals. In particular, immunogenic cell death (ICD) is accompanied by exposure release numerous damage-associated molecular patterns (DAMPs), altogether confer a robust adjuvanticity dying cancer cells, they favor recruitment activation antigen-presenting cells. ICD-associated DAMPs include surface-exposed calreticulin (CALR) secreted ATP, annexin A1 (ANXA1), type I interferon, high-mobility group box 1 (HMGB1). Additional hallmarks ICD encompass phosphorylation eukaryotic translation initiation factor 2 subunit-α (EIF2S1, better known eIF2α), autophagy, global arrest in transcription translation. Here, we outline methodological approaches for measuring markers vitro ex vivo discovery next-generation antineoplastic agents, development personalized regimens, identification optimal therapeutic combinations clinical management cancer.

Language: Английский

Citations

766
The complex role of tumor-infiltrating macrophages DOI
Anthos Christofides, Laura Strauss, Alan T. Yeo

et al.

Nature Immunology, Journal Year: 2022, Volume and Issue: 23(8), P. 1148 - 1156

Published: July 25, 2022

Language: Английский

Citations

507
The adenosine pathway in immuno-oncology DOI
Bertrand Allard, David Allard, Laurence Buisseret

et al.

Nature Reviews Clinical Oncology, Journal Year: 2020, Volume and Issue: 17(10), P. 611 - 629

Published: June 8, 2020

Language: Английский

Citations

411
Myeloid immunosuppression and immune checkpoints in the tumor microenvironment DOI Open Access
Kyohei Nakamura, Mark J. Smyth

Cellular and Molecular Immunology, Journal Year: 2019, Volume and Issue: 17(1), P. 1 - 12

Published: Oct. 14, 2019

Language: Английский

Citations

407
Multidrug Resistance in Cancer: Understanding Molecular Mechanisms, Immunoprevention and Therapeutic Approaches DOI Creative Commons
Talha Bin Emran, Asif Shahriar, Aar Rafi Mahmud

et al.

Frontiers in Oncology, Journal Year: 2022, Volume and Issue: 12

Published: June 23, 2022

Cancer is one of the leading causes death worldwide. Several treatments are available for cancer treatment, but many treatment methods ineffective against multidrug-resistant cancer. Multidrug resistance (MDR) represents a major obstacle to effective therapeutic interventions This review describes known MDR mechanisms in cells and discusses ongoing laboratory approaches novel strategies that aim inhibit, circumvent, or reverse development various types. In this review, we discuss both intrinsic acquired drug resistance, addition highlighting hypoxia- autophagy-mediated mechanisms. factors, including individual genetic differences, such as mutations, altered epigenetics, enhanced efflux, cell inhibition, other molecular cellular mechanisms, responsible anticancer agents. Drug can also depend on autophagic hypoxic status. The expression drug-resistant genes regulatory determine discussed. Methods circumvent MDR, immunoprevention, use microparticles nanomedicine might result better fighting

Language: Английский

Citations

359
Targeting Adenosine in Cancer Immunotherapy to Enhance T-Cell Function DOI Creative Commons
Selena Viganó, Dimitrios Alatzoglou, Melita Irving

et al.

Frontiers in Immunology, Journal Year: 2019, Volume and Issue: 10

Published: June 6, 2019

T cells play a critical role in cancer control, but range of potent immunosuppressive mechanisms can be upregulated the tumor microenvironment (TME) to abrogate their activity. While various immunotherapies (IMTs) aiming at re-invigorating T-cell-mediated anti-tumor response, such as immune checkpoint blockade (ICB), and adoptive cell transfer (ACT) natural or gene-engineered ex vivo expanded tumor-specific cells, have led unprecedented clinical responses, only small proportion patients benefit from these treatments. Important research efforts are thus underway identify biomarkers well develop personalized combinatorial approaches that target other inhibitory TME. In recent years, adenosinergic signaling has emerged powerful immuno-metabolic tumors. Like several barriers TME, PD-1/PDL-1 axis, CTLA-4, indoleamine 2,3-dioxygenase (IDO-1), adenosine plays important physiologic roles, been co-opted by tumors promote growth impair immunity. Several agents counteracting axis developed, pre-clinical studies demonstrated activity, alone combination with IMTs including ICB ACT. Here we review regulation levels which it promotes broadly suppresses protective immunity, extra focus on attenuation function. Finally, present an overview promising being explored for blocking enhanced control solid

Language: Английский

Citations

358
Extracellular vesicles as tools and targets in therapy for diseases DOI Creative Commons

Mudasir A. Kumar,

Sadaf Khursheed Baba,

Hana Q. Sadida

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Feb. 5, 2024

Abstract Extracellular vesicles (EVs) are nano-sized, membranous structures secreted into the extracellular space. They exhibit diverse sizes, contents, and surface markers ubiquitously released from cells under normal pathological conditions. Human serum is a rich source of these EVs, though their isolation proteins non-EV lipid particles poses challenges. These transport various cellular components such as proteins, mRNAs, miRNAs, DNA, lipids across distances, influencing numerous physiological events, including those within tumor microenvironment (TME). Their pivotal roles in communication make EVs promising candidates for therapeutic agents, drug delivery systems, disease biomarkers. Especially cancer diagnostics, EV detection can pave way early identification offers potential diagnostic Moreover, subtypes emerging targeted tools, highlighting clinical significance. The need non-invasive biomarkers to monitor biological processes purposes remains unfulfilled. Tapping unique composition could unlock advanced avenues future. In this review, we discuss detail conditions, cancers (encompassing head neck, lung, gastric, breast, hepatocellular carcinoma), neurodegenerative disorders, diabetes, viral infections, autoimmune renal diseases, emphasizing advancements molecular diagnostics delivery.

Language: Английский

Citations

352