Necroptosis in Immuno-Oncology and Cancer Immunotherapy

Cells, Journal Year: 2020, Volume and Issue: 9(8), P. 1823 - 1823

Published: Aug. 1, 2020

Immune-checkpoint blockers (ICBs) have revolutionized oncology and firmly established the subfield of immuno-oncology. Despite this renaissance, a subset cancer patients remain unresponsive to ICBs due widespread immuno-resistance. To “break” cell-driven immuno-resistance, researchers long floated idea therapeutically facilitating immunogenicity cells by disrupting tumor-associated immuno-tolerance via conventional anticancer therapies. It is well appreciated that therapies causing immunogenic or inflammatory cell death are best positioned productively activate immunity. A large proportion studies emphasized importance apoptosis (i.e., ICD); yet, it has also emerged necroptosis, programmed necrotic pathway, can be immunogenic. Emergence proficient immune profile for necroptosis important implications because resistance one major hallmarks tumors. Putative characteristics driven great impact in However, as typical highly complex multi-factorial disease like cancer, clear cause versus consensus relationship on immunobiology been tough establish. In review, we discuss various aspects with specific focus immuno-oncology immunotherapy.

Language: Английский

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Mitochondrial Dynamics, ROS, and Cell Signaling: A Blended Overview

Life, Journal Year: 2021, Volume and Issue: 11(4), P. 332 - 332

Published: April 10, 2021

Mitochondria are key intracellular organelles involved not only in the metabolic state of cell, but also several cellular functions, such as proliferation, Calcium signaling, and lipid trafficking. Indeed, these characterized by continuous events fission fusion which contribute to dynamic plasticity their network, strongly influenced mitochondrial contacts with other subcellular organelles. Nevertheless, mitochondria release a major amount reactive oxygen species (ROS) inside eukaryotic cells, reported mediate plethora both physiological pathological growth regulation autophagy, apoptosis, metastasis. Therefore, targeting ROS could be promising strategy overcome hinder development diseases cancer, where malignant possessing higher respect healthy ones, specifically targeted therapeutic treatments. In this review, we collected ultimate findings on blended interplay among shaping, ROS, signaling pathways, order dissection molecular mechanisms pathophysiology possibly improving future approaches.

Language: Английский

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Fueling the Fire: Inflammatory Forms of Cell Death and Implications for Cancer Immunotherapy

Cancer Discovery, Journal Year: 2021, Volume and Issue: 11(2), P. 266 - 281

Published: Jan. 15, 2021

Abstract Unleashing the immune system with checkpoint inhibitors (ICI) has significantly improved overall survival for subsets of patients stage III/IV cancer. However, many tumors are nonresponsive to ICIs, in part due a lack tumor-infiltrating lymphocytes (TIL). Converting these “cold” “hot” that thus more likely respond ICIs is major obstacle cancer treatment. Triggering inflammatory forms cell death, such as necroptosis and pyroptosis, may alter tumor microenvironment influx TILs. We present an emerging view promoting tumor-localized pyroptosis ultimately enhance responses ICI. Significance: Many types poorly or but subsequently acquire resistance. Effective therapies ICI-nonresponsive lacking should be guided by evidence from preclinical studies. Promoting death mechanisms within local toward ICI-responsive state.

Language: Английский

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Caspase‐3‐mediated GSDME induced Pyroptosis in breast cancer cells through the ROS/JNK signalling pathway

Journal of Cellular and Molecular Medicine, Journal Year: 2021, Volume and Issue: 25(17), P. 8159 - 8168

Published: Aug. 8, 2021

Pyroptosis is a new form of programmed cell death generated by some inflammasomes, piloting the cleavage gasdermin (GSDM) and stimulation dormant cytokines like IL-18 IL-1β; these reactions are narrowly linked to certain diseases diabetic nephropathy atherosclerosis. Doxorubicin, typical anthracycline, famous anticancer drug has emerged as prominent medication in several cancer chemotherapies, although its application accompanied with expending dose-dependent, increasing, irreversible continuing cardiotoxic side effects. However, exact path that links induced pyroptosis mechanism which Doxorubicin (DOX) acts against breast cells still puzzling. The present study seeks elucidate potential link between DOX-induced two human lines (MDA-MB-231 T47D). We proved treatment DOX reduced viability dose-dependent way morphology MDA-MB-231 T47D cells. Also, protein expression analyses revealed GSDME key regulator highlighted related role Caspase-3 activation. Furthermore, treatments intracellular accumulation ROS, stimulated phosphorylation JNK, activation, subsequently. In conclusion, suggests triggered caspase-3 dependent through ROS/JNK signalling pathway. Additionally, it showed cardiotoxicity can be minimized reducing level GSDME; thus, outcomes provide research target implications for investigations therapeutic applications.

Language: Английский

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Circulating tumor nucleic acids: biology, release mechanisms, and clinical relevance

Molecular Cancer, Journal Year: 2023, Volume and Issue: 22(1)

Published: Jan. 21, 2023

Despite advances in early detection and therapies, cancer is still one of the most common causes death worldwide. Since each tumor unique, there a need to implement personalized care develop robust tools for monitoring treatment response assess drug efficacy prevent disease relapse.

Language: Английский

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