Resisting T cell attack: tumor-cell-intrinsic defense and reparation mechanisms DOI Creative Commons
Brienne McKenzie, Salvatore Valitutti

Trends in cancer, Journal Year: 2022, Volume and Issue: 9(3), P. 198 - 211

Published: Dec. 31, 2022

Cytotoxic T lymphocytes (CTLs) are antigen-specific killer cells equipped to identify and eliminate host that have been altered through infection or transformation. Both chimeric antigen-receptor (CAR) cell therapies immune checkpoint blockade (ICB) based on successful elimination of tumor by cytotoxic effectors. In this opinion article, we outline cell-intrinsic mechanisms which defend against CTLs, highlighting pathways confer resistance proposing opportunities for combination therapies. We discuss how exogenous killing entities [e.g., supramolecular attack particles (SMAPs)] offer a novel strategy circumvent cellular mechanisms. Our article highlights the importance identifying, quantifying, targeting defense at interface between CTLs as critical consideration in development immunotherapy approaches.

Language: Английский

Pleiotropic effects of mitochondria in aging DOI Open Access
Tanes Lima, Terytty Yang Li, Adrienne Mottis

et al.

Nature Aging, Journal Year: 2022, Volume and Issue: 2(3), P. 199 - 213

Published: March 17, 2022

Language: Английский

Citations

163
Herpesvirus infections and post-COVID-19 manifestations: a pilot observational study DOI Open Access
Світлана Зубченко, Iryna Kril, Олена Надіжко

et al.

Rheumatology International, Journal Year: 2022, Volume and Issue: 42(9), P. 1523 - 1530

Published: June 1, 2022

Language: Английский

Citations

111
Vaccine-boosted CAR T crosstalk with host immunity to reject tumors with antigen heterogeneity DOI Creative Commons
Leyuan Ma,

Alexander Hostetler,

Duncan M. Morgan

et al.

Cell, Journal Year: 2023, Volume and Issue: 186(15), P. 3148 - 3165.e20

Published: July 1, 2023

Chimeric antigen receptor (CAR) T cell therapy effectively treats human cancer, but the loss of recognized by CAR poses a major obstacle. We found that in vivo vaccine boosting cells triggers engagement endogenous immune system to circumvent antigen-negative tumor escape. Vaccine-boosted promoted dendritic (DC) recruitment tumors, increased uptake DCs, and elicited priming anti-tumor cells. This process was accompanied shifts metabolism toward oxidative phosphorylation (OXPHOS) critically dependent on CAR-T-derived IFN-γ. Antigen spreading (AS) induced vaccine-boosted enabled proportion complete responses even when initial 50% negative, heterogeneous control further enhanced genetic amplification IFN-γ expression. Thus, CAR-T-cell-derived plays critical role promoting AS, provides clinically translatable strategy drive such against solid tumors.

Language: Английский

Citations

97
Bioorthogonal photocatalytic proximity labeling in primary living samples DOI Creative Commons
Ziqi Liu,

Fuhu Guo,

Yufan Zhu

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: March 28, 2024

Abstract In situ profiling of subcellular proteomics in primary living systems, such as native tissues or clinic samples, is crucial for understanding life processes and diseases, yet challenging due to methodological obstacles. Here we report CAT-S, a bioorthogonal photocatalytic chemistry-enabled proximity labeling method, that expands wide range samples mitochondrial proteomes. Powered by our thioQM warhead development targeted chemistry, CAT-S enables the proteins cells with high efficiency specificity. We apply diverse cell cultures, dissociated mouse well T from human blood, portraying native-state proteomic characteristics, unveiled hidden (PTPN1, SLC35A4 uORF, TRABD). Furthermore, allows quantification perturbations on dysfunctional tissues, exampled diabetic kidneys, revealing alterations lipid metabolism may drive disease progression. Given advantages non-genetic operation, generality, spatiotemporal resolution, open exciting avenues investigations are otherwise inaccessible.

Language: Английский

Citations

19
How to improve photodynamic therapy-induced antitumor immunity for cancer treatment? DOI Creative Commons
Min Zhang, Yifan Zhao, He Ma

et al.

Theranostics, Journal Year: 2022, Volume and Issue: 12(10), P. 4629 - 4655

Published: Jan. 1, 2022

Photodynamic therapy (PDT) is a promising method of tumor ablation and function-preserving oncological intervention, which minimally invasive, repeatable, has excellent function cosmetic effect, with no cumulative toxicity.More importantly, PDT can induce immunogenic cell death local inflammation, thus stimulating the body's immune response.However, weak immunity induced by alone insufficient to trigger systemic response towards cancer cells.To overcome this obstacle, multiple strategies have been investigated, including microenvironment remodeling, vaccines, subcellular-targeted PDT, synergistic therapies.This review summarizes latest progress in development improve PDT-induced effect for enhanced treatment.

Language: Английский

Citations

61
The Expanding Arsenal of Cytotoxic T Cells DOI Creative Commons
Chiara Cassioli, Cosima T. Baldari

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: April 20, 2022

Cytotoxic T cells (CTLs) are the main cellular mediators of adaptive immune defenses against intracellular pathogens and malignant cells. Upon recognition specific antigen on their target, CTLs assemble an immunological synapse where they mobilise killing machinery that is released into synaptic cleft to orchestrate demise cell target. The arsenal stored in lysosome-like organelles undergo exocytosis response signals triggered by receptor following recognition. These include lytic granules carrying a cargo cytotoxic proteins packed proteoglycan scaffold, multivesicular bodies death ligand FasL, recently discovered supramolecular attack particles carry core encased non-membranous glycoprotein shell. Here we will briefly review features these entities discuss interrelationship interplay CTL-mediated killing.

Language: Английский

Citations

57
CD38 reduces mitochondrial fitness and cytotoxic T cell response against viral infection in lupus patients by suppressing mitophagy DOI Creative Commons
Ping-Min Chen,

Eri Katsuyama,

Abhigyan Satyam

et al.

Science Advances, Journal Year: 2022, Volume and Issue: 8(24)

Published: June 15, 2022

Infection is one of the major causes mortality in patients with systemic lupus erythematosus (SLE). We previously found that CD38, an ectoenzyme regulates production NAD + , up-regulated CD8 T cells SLE and correlates risk infection. Here, we report CD38 reduces cell function by negatively affecting mitochondrial fitness through inhibition multiple steps mitophagy, a process critical for mitochondria quality control. Using murine model, administration inhibitor cell–targeted manner reinvigorated their effector function, reversed defects autophagy mitochondria, improved viral clearance. conclude represents target to mitigate infection rates people SLE.

Language: Английский

Citations

55
Dynamic mitochondrial transcription and translation in B cells control germinal center entry and lymphomagenesis DOI Creative Commons
Yavuz F. Yazicioglu,

Eros Marin,

Ciaran Sandhu

et al.

Nature Immunology, Journal Year: 2023, Volume and Issue: 24(6), P. 991 - 1006

Published: April 24, 2023

Germinal center (GC) B cells undergo proliferation at very high rates in a hypoxic microenvironment but the cellular processes driving this are incompletely understood. Here we show that mitochondria of GC highly dynamic, with significantly upregulated transcription and translation associated activity factor A, mitochondrial (TFAM). TFAM, while also necessary for normal cell development, is required entry activated precursor into germinal reaction; deletion Tfam impairs formation, function output. Loss TFAM compromises actin cytoskeleton motility response to chemokine signaling, leading their spatial disorganization. We lymphoma substantially increases protective against development c-Myc transgenic mouse model. Finally, pharmacological inhibition inhibits growth GC-derived human induces similar defects cytoskeleton.

Language: Английский

Citations

43
Bridging live-cell imaging and next-generation cancer treatment DOI
María Alieva, Amber K. L. Wezenaar, Ellen J. Wehrens

et al.

Nature reviews. Cancer, Journal Year: 2023, Volume and Issue: 23(11), P. 731 - 745

Published: Sept. 13, 2023

Language: Английский

Citations

38
Knockout or inhibition of USP30 protects dopaminergic neurons in a Parkinson’s disease mouse model DOI Creative Commons
Tracy-Shi Zhang Fang, Yu Sun, Andrew C. Pearce

et al.

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Nov. 13, 2023

Abstract Mutations in SNCA, the gene encoding α-synuclein (αSyn), cause familial Parkinson’s disease (PD) and aberrant αSyn is a key pathological hallmark of idiopathic PD. This α-synucleinopathy leads to mitochondrial dysfunction, which may drive dopaminergic neurodegeneration. PARKIN PINK1, mutated autosomal recessive PD, regulate preferential autophagic clearance dysfunctional mitochondria (“mitophagy”) by inducing ubiquitylation proteins, process counteracted deubiquitylation via USP30. Here we show that loss USP30 Usp30 knockout mice protects against behavioral deficits increased mitophagy, decreased phospho-S129 αSyn, attenuation SN neuronal induced αSyn. These observations were recapitulated with potent, selective, brain-penetrant inhibitor, MTX115325, good drug-like properties. data strongly support further study inhibition as potential disease-modifying therapy for

Language: Английский

Citations

36