The cancer-immunity cycle: Indication, genotype, and immunotype

Immunity, Journal Year: 2023, Volume and Issue: 56(10), P. 2188 - 2205

Published: Oct. 1, 2023

The cancer-immunity cycle provides a framework to understand the series of events that generate anti-cancer immune responses. It emphasizes iterative nature response where killing tumor cells by T initiates subsequent rounds antigen presentation and cell stimulation, maintaining active immunity adapting it evolution. Any step can become rate-limiting, rendering system unable control growth. Here, we update based on remarkable progress past decade. Understanding mechanism checkpoint inhibition has evolved, as our view dendritic in sustaining anti-tumor immunity. We additionally account for role microenvironment facilitating, not just suppressing, response, discuss importance considering tumor's immunological phenotype, "immunotype". While these new insights add some complexity cycle, they also provide targets research therapeutic intervention.

Language: Английский

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CD8+ T cells in the cancer-immunity cycle

Immunity, Journal Year: 2023, Volume and Issue: 56(10), P. 2231 - 2253

Published: Oct. 1, 2023

Language: Английский

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Role of NEK2 in tumorigenesis and tumor progression

Trends in Molecular Medicine, Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 1, 2024

Never in mitosis A (NIMA)-related kinase 2 (NEK2) is a serine/threonine found the nucleus and cytoplasm throughout cell cycle. NEK2 overexpressed many cancers biomarker of poor prognosis. Factors contributing to elevation cancer cells include oncogenic transcription factors, decreased ubiquitination, DNA methylation, circular RNA (circRNA)/long noncoding (lncRNA)-miRNA axis. overexpression produces chromosomal instability aneuploidy, thereby enhancing progression suppressing antitumor immunity, which highlights prominence tumorigenesis tumor progression. Small-molecule inhibitors targeting have demonstrated promising therapeutic potential vitro vivo across various types. This review outlines regulatory mechanisms expression, emphasizes its functional roles initiation progression, anticancer properties inhibitors.

Language: Английский

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The Bright Future of mRNA as a Therapeutic Molecule

Genes, Journal Year: 2025, Volume and Issue: 16(4), P. 376 - 376

Published: March 26, 2025

The rapid success of messenger (m) RNA vaccines against COVID-19 has pushed the mRNA to forefront drug research. promise mRNA-based therapeutics and in other areas is not new but now emerging stronger. We review basic concepts, key historical aspects, recent research on as a therapeutic molecule fight infectious diseases cancer. also show current patent perspective this field. Altogether, we describe that technology rapidly moving field aiming for bright future.

Language: Английский

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In vivo armed macrophages curb liver metastasis through tumor-reactive T-cell rejuvenation

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: April 11, 2025

Despite recent progress in cancer treatment, liver metastases persist as an unmet clinical need. Here, we show that arming and tumor-associated macrophages vivo to co-express tumor antigens (TAs), IFNα, IL-12 unleashes robust anti-tumor immune responses, leading the regression of metastases. Mechanistically, armed expand reactive CD8+ T cells, which acquire features progenitor exhausted cells kill independently CD4+ cell help. IFNα produced by reprogram antigen presenting rewire cellular interactions, rescuing functions. In trigger immunity distinct metastasis mouse models colorectal melanoma, expressing either surrogate antigens, naturally occurring neoantigens or antigens. Altogether, our findings support translational potential rejuvenate for treatment

Language: Английский

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Exploring the Molecular Tumor Microenvironment and Translational Biomarkers in Brain Metastases of Non-Small-Cell Lung Cancer

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(4), P. 2044 - 2044

Published: Feb. 7, 2024

Brain metastases represent a significant clinical challenge in the treatment of non-small-cell lung cancer (NSCLC), often leading to severe decline patient prognosis and survival. Recent advances imaging systemic treatments have increased detection rates brain metastases, yet outcomes remain dismal due complexity metastatic tumor microenvironment (TME) lack specific biomarkers for early targeted therapy. The intricate interplay between NSCLC cells surrounding TME is pivotal, influencing progression, immune evasion, response This underscores necessity deeper understanding molecular underpinnings microenvironment, identification actionable that can inform multimodal approaches. goal this review synthesize current insights into elucidate mechanisms metastases. Furthermore, we will explore promising horizon emerging biomarkers, both tissue- liquid-based, hold potential radically transform strategies enhancement outcomes.

Language: Английский

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Tumour-intrinsic endomembrane trafficking by ARF6 shapes an immunosuppressive microenvironment that drives melanomagenesis and response to checkpoint blockade therapy

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

Published: Aug. 4, 2024

Tumour-host immune interactions lead to complex changes in the tumour microenvironment (TME), impacting progression, metastasis and response therapy. While it is clear that cancer cells can have capacity alter landscapes, our understanding of this process incomplete. Herein we show endocytic trafficking at plasma membrane, mediated by small GTPase ARF6, enables melanoma impose an immunosuppressive TME accelerates development. This ARF6-dependent vulnerable checkpoint blockade therapy (ICB) but murine melanoma, loss Arf6 causes resistance ICB. Likewise, downregulation ARF6 patient tumours correlates with inferior overall survival after Mechanistically, these phenotypes are least partially explained recycling, which controls membrane density interferon-gamma receptor. Collectively, findings reveal importance endomembrane outfitting ability shape their respond immunotherapy. The known regulate endocytosis recycling proteins. Here authors tumourintrinsic promotes progression blockade, mechanistically linked receptors cells.

Language: Английский

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CRY1 fuels resistance to T cell-based immunotherapy in NANOGhigh cancers

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 8, 2025

Cancer immunotherapies, including immune checkpoint blockade (ICB), have marked a significant breakthrough in cancer treatment but their clinical efficacy is limited immune-resistant tumors. Previously, we found that immunotherapy-mediated selection enriches tumors with both tumor-intrinsic and -extrinsic refractory phenotypes via the transcriptional induction of HDAC1 by NANOG. Here, identify CRY1 as critical target NANOG stabilizes Cyclin A MCL1 to promote stem cell-like property resistance cytotoxic T cell-mediated killing NANOG^high tumor cells through HDAC1-mediated epigenetic silencing APC3 TRIM17. Additionally, downregulates CXCL10 repression, thereby suppressing cell infiltration. Importantly, inhibition synergizes PD-1 adoptive transfer reducing growth converting into immune-sensitive Collectively, these findings highlight mediator NANOG/HDAC1 axis multiple properties suggest potential therapeutic target.

Language: Английский

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C9orf50 is a Targetable Spliceosome Regulator for Cancer Immunotherapy

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: March 15, 2025

Abstract Cancer cells harbor cell-intrinsic programs capable of sculpting immunogenic landscapes, yet molecular brakes that enforce immune evasion remain poorly defined. Here, we identify C9ORF50, a previously uncharacterized intrinsically disordered protein, as liquid-liquid phase separation-driven regulator RNA processing and actionable immunotherapy target. Genetic ablation C9ORF50 induces selective intron retention in spliceosome component transcripts, leading to cytoplasmic accumulation double-stranded (dsRNA). This dsRNA activates type I interferon pathway turn orchestrates chemokine secretory program critical for T cell recruitment. The resultant enhancement tumor immunogenicity reprogramming microenvironment drives robust antitumor immunity, effectively converting immunologically “cold” tumors “hot” phenotypes. Therapeutic targeting via interference achieved suppression syngeneic models, suggesting its translational relevance. Notably, exhibits tumor-predominant expression, with minimal baseline levels detected healthy tissues or populations, underscoring potential safety therapeutic Our study not only identifies novel LLPS-dependent splicing but also establishes it promising potentially safe target cancer immunotherapy.

Language: Английский

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eIF4F-mediated Dysregulation of mRNA Translation in Cancer

RNA, Journal Year: 2025, Volume and Issue: unknown, P. rna.080340.124 - rna.080340.124

Published: Jan. 14, 2025

Messenger RNA (mRNA) translational control plays a pivotal role in regulating cellular proteostasis under physiological and pathological conditions. Dysregulated mRNA translation is pervasive cancer, which protein synthesis elevated to support accelerated cell growth proliferation. Consequently, targeting the machinery has emerged as therapeutic strategy treat cancer. In this perspective, we summarize current knowledge of dysregulation with emphasis on eukaryotic initiation factor 4F (eIF4F) complex. We outline recent endeavors apply develop novel treatment strategies combat

Language: Английский

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