Tumor accomplice: T cell exhaustion induced by chronic inflammation DOI Creative Commons

Liguang Fang,

Kunjing Liu,

Cun Liu

et al.

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

Published: Sept. 2, 2022

The development and response to treatment of tumor are modulated by inflammation, chronic inflammation promotes progression therapy resistance. This article summarizes the dynamic evolution from acute in process development, its effect on T cells activation promotion exhaustion. We review mechanisms which inflammatory cytokines regulate cell exhaustion methods for targeting improve efficacy immunotherapy. It is great significance refer specific state at different stages accurate clinical decision-making immunotherapy improving efficiency

Language: Английский

T-cell dysfunction in the glioblastoma microenvironment is mediated by myeloid cells releasing interleukin-10 DOI Creative Commons
Vidhya M. Ravi, Nicolas Neidert, Paulina Will

et al.

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: Feb. 17, 2022

Despite recent advances in cancer immunotherapy, certain tumor types, such as Glioblastomas, are highly resistant due to their microenvironment disabling the anti-tumor immune response. Here we show, by applying an in-silico multidimensional model integrating spatially resolved and single-cell gene expression data of 45,615 cells from 12 samples, that a subset Interleukin-10-releasing HMOX1

Language: Английский

Citations

207
The advent of immune stimulating CAFs in cancer DOI
Maria Tsoumakidou

Nature reviews. Cancer, Journal Year: 2023, Volume and Issue: 23(4), P. 258 - 269

Published: Feb. 17, 2023

Language: Английский

Citations

80
BLIMP1 and NR4A3 transcription factors reciprocally regulate antitumor CAR T cell stemness and exhaustion DOI

In-Young Jung,

Vivek Narayan,

Sierra McDonald

et al.

Science Translational Medicine, Journal Year: 2022, Volume and Issue: 14(670)

Published: Nov. 9, 2022

Chimeric antigen receptor (CAR) T cells have not induced meaningful clinical responses in solid tumors. Loss of cell stemness, poor expansion capacity, and exhaustion during prolonged tumor exposure are major causes CAR therapeutic resistance. Single-cell RNA-sequencing analysis from a first-in-human trial metastatic prostate cancer identified two independently validated states associated with antitumor potency or lack efficacy. Low expression PRDM1 , encoding the BLIMP1 transcription factor, defined highly potent TCF7 [encoding factor 1 (TCF1)]–expressing CD8 + cells, whereas enrichment HAVCR2 immunoglobulin mucin-domain containing-3 (TIM-3)]–expressing elevated was outcomes. knockout promoted -dependent stemness proliferation, resulting marginally enhanced leukemia control mice. However, setting deficiency, negative epigenetic feedback program nuclear activated (NFAT)–driven dysfunction identified. This characterized by compensatory up-regulation NR4A3 other genes exhaustion-related factors that hampered effector function Dual skewed phenotypes away TIM-3 toward TCF1 to counter tumor-infiltrating improve responses, effects were achieved single alone. These data underscore dual targeting as promising approach advance adoptive immuno-oncotherapy.

Language: Английский

Citations

74
Lineage tracing reveals clonal progenitors and long-term persistence of tumor-specific T cells during immune checkpoint blockade DOI Creative Commons
Joy A. Pai, Matthew D. Hellmann, Jennifer L. Sauter

et al.

Cancer Cell, Journal Year: 2023, Volume and Issue: 41(4), P. 776 - 790.e7

Published: March 30, 2023

Language: Английский

Citations

74
Stepwise activities of mSWI/SNF family chromatin remodeling complexes direct T cell activation and exhaustion DOI Creative Commons
Elena Battistello,

Kimberlee A. Hixon,

Dawn E. Comstock

et al.

Molecular Cell, Journal Year: 2023, Volume and Issue: 83(8), P. 1216 - 1236.e12

Published: March 20, 2023

Highly coordinated changes in gene expression underlie T cell activation and exhaustion. However, the mechanisms by which such programs are regulated how these may be targeted for therapeutic benefit remain poorly understood. Here, we comprehensively profile genomic occupancy of mSWI/SNF chromatin remodeling complexes throughout acute chronic stimulation, finding that stepwise localization over transcription factor binding sites direct site-specific accessibility leading to distinct phenotypes. Notably, perturbation using genetic clinically relevant chemical strategies enhances persistence cells with attenuated exhaustion hallmarks increased memory features vitro vivo. Finally, pharmacologic inhibition improves CAR-T expansion results improved anti-tumor control These findings reveal central role coordination nominate small-molecule-based improvement current immunotherapy protocols.

Language: Английский

Citations

44
Integrative analysis of neuroblastoma by single-cell RNA sequencing identifies the NECTIN2-TIGIT axis as a target for immunotherapy DOI Creative Commons
Judith Wienke, Lindy L. Visser, Waleed M. Kholosy

et al.

Cancer Cell, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 1, 2024

Pediatric patients with high-risk neuroblastoma have poor survival rates and urgently need more effective treatment options less side effects. Since novel improved immunotherapies may fill this need, we dissect the immunoregulatory interactions in by single-cell RNA-sequencing of 24 tumors (10 pre- 14 post-chemotherapy, including 5 pairs) to identify strategies for optimizing immunotherapy efficacy. Neuroblastomas are infiltrated natural killer (NK), T B cells, immunosuppressive myeloid populations. NK cells show reduced cytotoxicity a dysfunctional profile. Interaction analysis reveals vast network identifies NECTIN2-TIGIT as crucial immune checkpoint. Combined blockade TIGIT PD-L1 significantly reduces growth, complete responses (CR) vivo. Moreover, addition TIGIT+PD-L1 standard relapse chemotherapy-resistant Th-ALKF1174L/MYCN 129/SvJ syngeneic model induces CR. In conclusion, our integrative provides promising targets rationale immunotherapeutic combination strategies.

Language: Английский

Citations

39
Biological and clinical significance of tumour-infiltrating lymphocytes in the era of immunotherapy: a multidimensional approach DOI
Miguel López de Rodas, María Villalba, Miguel F. Sanmamed

et al.

Nature Reviews Clinical Oncology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 16, 2025

Language: Английский

Citations

7
CD4+ Cytotoxic T cells – Phenotype, Function and Transcriptional Networks Controlling Their Differentiation Pathways DOI
Teresa Preglej, Wilfried Ellmeier

Immunology Letters, Journal Year: 2022, Volume and Issue: 247, P. 27 - 42

Published: May 11, 2022

Language: Английский

Citations

46
Exosomal cargos-mediated metabolic reprogramming in tumor microenvironment DOI Creative Commons

Shiming Tan,

Yiqing Yang, Wenjuan Yang

et al.

Journal of Experimental & Clinical Cancer Research, Journal Year: 2023, Volume and Issue: 42(1)

Published: March 10, 2023

Metabolic reprogramming is one of the hallmarks cancer. As nutrients are scarce in tumor microenvironment (TME), cells adopt multiple metabolic adaptations to meet their growth requirements. not only present cells, but exosomal cargos mediates intercellular communication between and non-tumor TME, inducing remodeling create an outpost microvascular enrichment immune escape. Here, we highlight composition characteristics meanwhile summarize components corresponding sorting mode. Functionally, these cargos-mediated improves "soil" for metastasis. Moreover, discuss abnormal metabolism targeted by its potential antitumor therapy. In conclusion, this review updates current role TME enriches future application scenarios exosomes.

Language: Английский

Citations

42
N-acetylneuraminic acid links immune exhaustion and accelerated memory deficit in diet-induced obese Alzheimer’s disease mouse model DOI Creative Commons
Stefano Suzzi, Tommaso Croese,

Adi Ravid

et al.

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

Published: March 9, 2023

Abstract Systemic immunity supports lifelong brain function. Obesity posits a chronic burden on systemic immunity. Independently, obesity was shown as risk factor for Alzheimer’s disease (AD). Here we show that high-fat obesogenic diet accelerated recognition-memory impairment in an AD mouse model (5xFAD). In obese 5xFAD mice, hippocampal cells displayed only minor diet-related transcriptional changes, whereas the splenic immune landscape exhibited aging-like CD4 + T-cell deregulation. Following plasma metabolite profiling, identified free N -acetylneuraminic acid (NANA), predominant sialic acid, linking to increased immune-suppressive mice. Single-nucleus RNA-sequencing revealed visceral adipose macrophages potential source of NANA. vitro, NANA reduced proliferation, tested both and human. vivo, administration standard diet-fed mice recapitulated effects T We suggest accelerates manifestation via exhaustion.

Language: Английский

Citations

26