BAAT away liver cancer: conjugated bile acids impair T cell function in hepatocellular carcinoma immunotherapy DOI Open Access
Zachary Detwiler, Snehal N. Chaudhari

Immunometabolism, Journal Year: 2025, Volume and Issue: 7(2), P. e00062 - e00062

Published: April 1, 2025

In this renaissance era of gene therapy, a new study published by the Susan Kaech lab in Science demonstrates use CRISPR-Cas9 technology to selectively deplete conjugated bile acids liver targeting acid–CoA:amino acid N -acyltransferase ( Baat ) improve responsiveness immunotherapy. This highlights role impairing intratumoral T cell function directly accumulating resident cells and driving mitochondrial dysfunction. Knockout reduced hepatic production, thus improving immunotherapy potency reducing tumor burden. Subsequently, knockout levels microbially produced secondary such as lithocholic acid, known carcinogen toxin. mechanistically links cancer success, setting stage for acid-based screening approaches pharmacologic manipulations improved patient outcomes.

Language: Английский

Injecting hope: the potential of intratumoral immunotherapy for locally advanced and metastatic cancer DOI Creative Commons
Markéta Skaličková, Katerina Hadrava Vanova, Ondřej Uher

et al.

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 9, 2025

Despite enormous progress, advanced cancers are still one of the most serious medical problems in current society. Although various agents and therapeutic strategies with anticancer activity known used, they often fail to achieve satisfactory long-term patient outcomes survival. Recently, immunotherapy has shown success patients by harnessing important interactions between immune system cancer. However, many these therapies lead frequent side effects when administered systemically, prompting treatment modifications or discontinuation or, severe cases, fatalities. New approaches like intratumoral immunotherapy, characterized reduced effects, cost, systemic toxicity, offer promising prospects for future applications clinical oncology. In context locally metastatic cancer, combining diverse immunotherapeutic other targeting multiple cancer hallmarks appears crucial. Such combination hold promise improving survival promoting a sustained response. This review aims provide overview approaches, specifically focusing on administration drugs cancers. It also explores integration modalities maximize Additionally, summarizes recent advances discusses novel outlining directions field.

Language: Английский

Citations

3
Advances in Cell and Immune Therapies for Melanoma DOI Creative Commons

Tanase Timis,

Sanda Buruiana, Delia Dima

et al.

Biomedicines, Journal Year: 2025, Volume and Issue: 13(1), P. 98 - 98

Published: Jan. 3, 2025

The incidence rate of cutaneous melanoma is on the rise worldwide, due to increased exposure UV radiation, aging populations, and teratogen agents. However, diagnosis more precise, number new cases related improved tools. Despite better early therapies, has remained a significant public health challenge because its aggressive behavior high potential for metastasis. In 2020, constituted approximately 1.3% all cancer deaths that occurred within European Union, thereby highlighting necessity effective prevention, timely diagnosis, sustainable treatment measures, especially as growing occur among younger patients. Melanoma regarded one most inflamed cancers immune cell presence strong response immunotherapy, fueling need development immune-driven innovative treatments. Approved including checkpoint inhibitors (e.g., anti-PD-1 anti-CTLA-4), have notably survival rates in melanoma. limitations PD-1/PD-L1 CTLA-4 axes inhibitors, such low rates, resistance, toxicity, driven continued research advancements strategies. Current clinical trials are exploring various combinations with costimulatory receptor agonists, chemotherapy, targeted other immunotherapies, goal improving outcomes reducing side effects Emerging approaches, adoptive therapy tumor-infiltrating lymphocytes (TILs) oncolytic virotherapy, showing promise. While CAR-T been less successful compared blood cancers, ongoing addressing challenges like tumor microenvironment antigen specificity. This review provides an overview requirement advances these medications, mark step forward management, set bring fresh breath hope

Language: Английский

Citations

2
Allogeneic chimeric antigen receptor cell therapies for cancer: progress made and remaining roadblocks DOI
Caroline Diorio, David T. Teachey, Stephan A. Grupp

et al.

Nature Reviews Clinical Oncology, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 15, 2024

Language: Английский

Citations

10
Chimeric Cytokine Receptor TGF-β RⅡ/IL-21R Improves CAR-NK Cell Function by Reversing the Immunosuppressive Tumor Microenvironment of Gastric Cancer DOI Creative Commons

Yaojun Ren,

Min Xue,

Xinhui Hui

et al.

Pharmacological Research, Journal Year: 2025, Volume and Issue: 212, P. 107637 - 107637

Published: Jan. 29, 2025

Gastric cancer remains a significant global health burden, characterized by regional variations in incidence and poor survival prospects advanced stages. Natural killer (NK) cells play crucial role the body's anti-cancer defense, chimeric antigen receptor (CAR)-NK cell therapy is gaining attention as cutting-edge promising treatment method. This study aims to tackle challenge of TGF-β-mediated tumor immune evasion within immunosuppressive microenvironment designing novel cytokine TRII/21R, which consists extracellular domains TGF-β II (TRII) transmembrane intracellular IL-21 (21R) can convert signal from (TME) into an NK activation through IL-21R-STAT3 pathway. We successfully constructed NKG2D-CAR-NK expressing TRII/21R demonstrated strong anti-tumor activity against both vitro vivo. The co-expression CAR-NK enhanced cytotoxicity, promoted proliferation capabilities, reduced expression exhaustion markers. In xenograft mouse model, TRII/21R-CAR-NK significantly inhibited growth improved rate tumor-bearing mice compared receiving control cells. Additionally, cells' infiltration, activation, persistence tumor, indicating robust response mediated JAK-STAT3 signaling underscores therapeutic potential TRII/21R-modified breakthrough strategy for combating cancer.

Language: Английский

Citations

2
SMAD4 Regulates the Expression of LCK Affecting Chimeric Antigen Receptor‐T Cells Proliferation Through PI3K/Akt Signaling Pathway DOI Creative Commons
Rongxue Wan, Bowen Fu, Xuemei Fu

et al.

Journal of Cellular Physiology, Journal Year: 2025, Volume and Issue: 240(1)

Published: Jan. 1, 2025

ABSTRACT The proliferation of CAR‐T cells was hindered and cannot play its killing function well in solid tumors. And yet the regulatory mechanism cell is not fully understood. Here, we showed that recombinant expression CD19CAR T significantly increased basal activation level LCK activation. Both SMAD4 were essential for since over‐express or promotes proliferation, while knock‐down inhibited seriously. More go into apoptosis when expression, cycle arrested G2/M S phase, respectively. Over‐express phosphorylation PI3K Akt, it treated with Akt inhibitors (LY294002 MK2206). Further exploration experiments bound on promoter region regulating expression. Taken together, reported transcription factor regulated further involved PI3K/Akt signaling pathway to affect cells.

Language: Английский

Citations

1
Translational study of the regulatory mechanism by which immune synapses enhance immune cell function DOI

Yahui Li,

Xiao‐Jun Huang, Xiang‐Yu Zhao

et al.

Cancer Letters, Journal Year: 2025, Volume and Issue: 614, P. 217542 - 217542

Published: Feb. 7, 2025

Language: Английский

Citations

1
Are monocytes a preferable option to develop myeloid cell-based therapies for solid tumors? DOI Creative Commons

Daisy Bhatia,

Riccardo Dolcetti, Roberta Mazzieri

et al.

Journal of Experimental & Clinical Cancer Research, Journal Year: 2025, Volume and Issue: 44(1)

Published: March 15, 2025

Abstract In the last two decades, novel and promising cell-based therapies have populated treatment landscape for haematological tumors. However, commonly exploited T NK show limited applicability to solid This is mainly given by impaired tumor trafficking capability effector activity of these cells within a highly immunosuppressive microenvironment. Myeloid spontaneously home tumors can thus be reprogrammed and/or engineered directly attack or locally selectively deliver therapeutically relevant payloads that may improve efficacy immunotherapy against difficult-to-access context myeloid therapies, adoptive transfer monocytes has often been overshadowed infusion differentiated macrophages hematopoietic stem cell transplantation despite their therapeutic potential. Here, we summarize recent improvements benefits using tumors, current clinical applications challenges use as well some possible strategies overcome them.

Language: Английский

Citations

1
Engineering innate immune cells for cancer immunotherapy DOI
Mubin Tarannum,

Xizhong Ding,

Marta Barisa

et al.

Nature Biotechnology, Journal Year: 2025, Volume and Issue: 43(4), P. 516 - 533

Published: April 1, 2025

Language: Английский

Citations

1
Evaluation of efficacy, safety and underlying mechanism on Traditional Chinese medicine as synergistic agents for cancer immunotherapy: A preclinical systematic review and meta-analysis DOI
Jing Li, Shipeng Fan, Hongxia Li

et al.

Journal of Ethnopharmacology, Journal Year: 2024, Volume and Issue: 338, P. 119035 - 119035

Published: Nov. 5, 2024

Language: Английский

Citations

6
Immune dynamics shaping pre-metastatic and metastatic niches in liver metastases: from molecular mechanisms to therapeutic strategies DOI Creative Commons
Chang Zhu,

J Liao,

Yiyang Liu

et al.

Molecular Cancer, Journal Year: 2024, Volume and Issue: 23(1)

Published: Nov. 14, 2024

Liver metastases are commonly detected in the advanced stages of various malignant tumors, representing a significant clinical challenge. Throughout process liver formation, immune cells play pivotal role, particularly pre-metastatic and metastatic niches within liver. Immune establish extensive intricate interactions with tumor other components liver, collectively promoting sustaining growth metastases. Despite limited efficacy existing therapeutic modalities against some metastases, novel immune-based treatment approaches continuously being explored validated. Building on systematic elucidation immunosuppressive characteristics we potential immunotherapies applicable to patients from multiple dimensions.

Language: Английский

Citations

4