Role ofCD47gene expression in colorectal cancer: a comprehensive molecular profiling study DOI Creative Commons
Hiroyuki Arai, Nishant Gandhi, Francesca Battaglin

et al.

Journal for ImmunoTherapy of Cancer, Journal Year: 2024, Volume and Issue: 12(11), P. e010326 - e010326

Published: Oct. 1, 2024

Background In patients with colorectal cancer (CRC), the therapeutic effects of conventional immune checkpoint inhibitors targeting adaptive system are largely limited to those microsatellite instability-high tumors. Meanwhile, new immunotherapies innate attracting increasing attention. CD47 is a representative involved in evasion tumor cell phagocytosis by macrophages. This large-scale study comprehensively examined molecular significance gene expression CRC. Methods We analyzed next-generation sequencing data DNA and RNA from 14,287 CRC cases included set commercial Clinical Laboratory Improvement Amendments-certified laboratory (Caris Life Sciences). The were divided into two groups based on median value levels. profiles between compared, relationship survival outcomes was further examined. Results -high tumors, proportion consensus subtypes 1 4 significantly higher than -low levels damage-associated pattern-related genes showed positive correlation Major oncogenic pathways, such as mitogen-activated protein kinase, phosphoinositide 3-kinase, angiogenesis, transforming growth factor beta, activated Additionally, panel estimates cells constituting microenvironment (TME) Conclusions associated activation several pathways an immune-engaged TME. Our findings may provide valuable information for considering strategies checkpoints

Language: Английский

Chemoproteomic discovery of a covalent allosteric inhibitor of WRN helicase DOI

Kristen A. Baltgalvis,

Kelsey N. Lamb,

Kent T. Symons

et al.

Nature, Journal Year: 2024, Volume and Issue: 629(8011), P. 435 - 442

Published: April 24, 2024

Language: Английский

Citations

33
Hallmarks of cancer resistance DOI Creative Commons
Muhammad Tufail,

Jia-Ju Hu,

Jie Liang

et al.

iScience, Journal Year: 2024, Volume and Issue: 27(6), P. 109979 - 109979

Published: May 15, 2024

This review explores the hallmarks of cancer resistance, including drug efflux mediated by ATP-binding cassette (ABC) transporters, metabolic reprogramming characterized Warburg effect, and dynamic interplay between cells mitochondria. The role stem (CSCs) in treatment resistance regulatory influence non-coding RNAs, such as long RNAs (lncRNAs), microRNAs (miRNAs), circular (circRNAs), are studied. chapter emphasizes future directions, encompassing advancements immunotherapy, strategies to counter adaptive integration artificial intelligence for predictive modeling, identification biomarkers personalized treatment. comprehensive exploration these provides a foundation innovative therapeutic approaches, aiming navigate complex landscape enhance patient outcomes.

Language: Английский

Citations

20
Understanding and overcoming resistance to immunotherapy in genitourinary cancers DOI Creative Commons

S. Evans,

Yash Jani,

Caroline S. Jansen

et al.

Cancer Biology & Therapy, Journal Year: 2024, Volume and Issue: 25(1)

Published: April 17, 2024

The introduction of novel immunotherapies has significantly transformed the treatment landscape genitourinary (GU) cancers, even becoming standard care in some settings. One such type immunotherapy, immune checkpoint inhibitors (ICIs) like nivolumab, ipilimumab, pembrolizumab, and atezolizumab play a pivotal role by disturbing signaling pathways that limit system's ability to fight tumor cells. Despite profound impact these treatments, not all tumors are responsive. Recent research efforts have been focused on understanding how cancer cells manage evade response identifying possible mechanisms behind resistance immunotherapy. In response, ICIs being combined with other treatments reduce attack through multiple cellular pathways. Additionally, novel, targeted strategies currently investigated develop innovative methods overcoming failure. This article presents comprehensive overview immunotherapy GU cancers as described literature. It explores studies identified genetic markers, cytokines, proteins may predict or we review current overcome this resistance, which include combination sequential therapies, insights into host profile, new therapies. Various approaches combine chemotherapy, therapy, vaccines, radiation studied an effort more effectively While each therapies shown efficacy clinical trials, deeper underscores potential particularly promising area research. Currently, several agents development, along identification key mediators involved resistance. Further is necessary identify predictors response.

Language: Английский

Citations

11
FSTL3 promotes tumor immune evasion and attenuates response to anti-PD1 therapy by stabilizing c-Myc in colorectal cancer DOI Creative Commons

Haiyang Li,

Na Zheng,

Anning Guo

et al.

Cell Death and Disease, Journal Year: 2024, Volume and Issue: 15(2)

Published: Feb. 1, 2024

Abstract Programmed cell death 1 ligand (PDL1)/programmed (PD1) blockade immunotherapy provides a prospective strategy for the treatment of colorectal cancer (CRC), but various constraints on effectiveness are still remaining. As reported in previous studies, follistatin-like 3 (FSTL3) could mediate inflammatory response macrophages by induction lipid accumulation. Herein, we revealed that FSTL3 were overexpressed malignant cells CRC microenvironment, notably, expression level was related to tumor immune evasion and clinical efficacy anti-PD1 therapy. Further studies determined hypoxic microenvironment induced via HIF1α cells, bind transcription factor c-Myc (354–406 amino acids) suppress latter’s ubiquitination increase its stability, thereby up-regulated PDL1 indoleamine 2,3-dioxygenase (IDO1). The results immunocompetent models verified FSLT3 knockout increased proportion CD8 + T reduced regulatory (CD25 Foxp3 ) exhausted (PD1 ), synergistically improved therapy efficacy. To sum up, enhanced c-Myc-mediated transcriptional regulation promote attenuates CRC, suggesting potential as biomarker immunotherapeutic well novel target CRC.

Language: Английский

Citations

9
Synergistically Enhanced Chemodynamic Therapy Induced by NIR-II Photothermal Therapy with MRI/CT Imaging Guidance for Colorectal Cancer DOI
Zhusheng Liu, Chengyuan Hong,

Chunshu Pan

et al.

ACS Materials Letters, Journal Year: 2024, Volume and Issue: 6(5), P. 1593 - 1605

Published: March 22, 2024

Chemodynamic therapy (CDT) exhibits unsatisfactory therapeutic efficacy for colorectal cancer (CRC) due to the hyposensitive Fenton reaction. Herein, we constructed a novel multifunctional nanoplatform based on bismuth-doped iron selenide nanoparticles (BFS NPs) promoting performance of CDT CRC. BFS NPs can realize and second near-infrared photothermal (NIR-II PTT) by means reaction an excellent conversion efficiency (η = 31.9%). Moreover, rising temperature induced NIR irradiation accelerates rate because there being more activated H2O2, thereby improving reactive oxygen species (ROS) levels address insufficient hydrogen peroxide concentration. The results showed that combination with NIR-II PTT significantly inhibits growth CRC minimizes adverse reactions. Meanwhile, bismuth doping endows superior CT imaging T2-weighted magnetic resonance (T2-MRI) capacities. These unique properties offer appropriate treatment time window guiding PTT. In summary, this improves effect accurately regulates MRI/CT guidance, which provides new perspective effective precise

Language: Английский

Citations

9
Cellular and molecular mechanisms of gastrointestinal cancer liver metastases and drug resistance DOI

Daosong Dong,

Yu Xue, Jingjing Xu

et al.

Drug Resistance Updates, Journal Year: 2024, Volume and Issue: 77, P. 101125 - 101125

Published: Aug. 6, 2024

Language: Английский

Citations

7
IL-2RG as a possible immunotherapeutic target in CRC predicting poor prognosis and regulated by miR-7-5p and miR-26b-5p DOI Creative Commons
Ehsan Gharib, Leili Rejali, Moein Piroozkhah

et al.

Journal of Translational Medicine, Journal Year: 2024, Volume and Issue: 22(1)

Published: May 8, 2024

Abstract Despite advances in treatment strategies, colorectal cancer (CRC) continues to cause significant morbidity and mortality, with mounting evidence a close link between immune system dysfunctions issued. Interleukin-2 receptor gamma (IL-2RG) plays pivotal role as common subunit the IL-2 family cytokines activates JAK-STAT pathway. This study delves into of within tumor microenvironment investigates potential microRNAs (miRNAs) that directly inhibit IL-2RG, aiming discern their impact on CRC clinical outcomes. Bioinformatics analysis revealed upregulation IL-2RG mRNA TCGA-COAD samples showed strong correlations infiltration various lymphocytes. Single-cell corroborated these findings, highlighting expression critical cell subsets. To explore miRNA involvement dysregulation, was isolated from tissues lymphocytes 258 patients 30 healthy controls, cloned pcDNA3.1/CT-GFP-TOPO vector. Human embryonic kidney lines (HEK-293T) were transfected this construct. Our research involved comprehensive miRPathDB, miRWalk, Targetscan databases identify miRNAs associated 3′ UTR human IL-2RG. The microRNA (miRNA) molecules, hsa-miR-7-5p hsa-miR-26b-5p, have been identified potent suppressors patients. Specifically, downregulation hsa-miR-26b-5p has shown result Prognostic evaluation hsa-miR-7-5p, using data patient samples, established higher lower both poorer Additionally, several long non-coding RNAs (LncRNAs), such ZFAS1, SOX21-AS1, SNHG11, SNHG16, SNHG1, DLX6-AS1, GAS5, SNHG6, MALAT1, which may act competing endogenous RNA molecules for IL2RG by sequestering shared hsa-miR-26b-5p. In summary, investigation underscores utility serum tissue biomarkers predicting prognosis while also offering promise targets immunotherapy management. Graphical

Language: Английский

Citations

5
Simultaneous inhibition of PD-1 and LAG-3: the future of immunotherapy? DOI
Sasha-Jane Abi-Aad, Joseph Zouein, Antoine Chartouni

et al.

Immunotherapy, Journal Year: 2023, Volume and Issue: 15(8), P. 611 - 618

Published: April 3, 2023

Immunotherapy has improved the prognosis of many cancers, yet a large number patients have demonstrated resistance to current immune checkpoint inhibitors. LAG-3 is an expressed on tumor-infiltrating lymphocytes CD4+ and CD8+, Tregs other cells. Coexpression PD-1 in solid or hematological cancers generally associated with poor may be responsible for immunotherapy resistance. Dual inhibition therapy RELATIVITY-047 trial significantly progression-free survival metastatic melanoma. This article discusses presence possible synergistic interaction between tumor microenvironment utility targeting both inhibitors as effective way bypass increase treatment efficacy.

Language: Английский

Citations

12
Colorectal cancer cell-derived exosomal miRNA-372-5p induces immune escape from colorectal cancer via PTEN/AKT/NF-κB/PD-L1 pathway DOI
Yulun Wu,

Yuhan Xiao,

Yongxing Ding

et al.

International Immunopharmacology, Journal Year: 2024, Volume and Issue: 143, P. 113261 - 113261

Published: Sept. 30, 2024

Language: Английский

Citations

4
Tumor-Intrinsic Cgas-Sting Pathway Activation Contributes to Fasting-Sensitized Immunotherapy in Colorectal Cancer DOI
Weichen Song, Zhaohui Tang, Donglin Zeng

et al.

Published: Jan. 1, 2025

Language: Английский

Citations

0