Hepatotoxicity in Cancer Immunotherapy: Diagnosis, Management, and Future Perspectives DOI Open Access

Alberto Savino,

A. Rossi, S. Fagiuoli

et al.

Cancers, Journal Year: 2024, Volume and Issue: 17(1), P. 76 - 76

Published: Dec. 29, 2024

Cancer immunotherapy, particularly immune checkpoint inhibitors, has positively impacted oncological treatments. Despite its effectiveness, immunotherapy is associated with immune-related adverse events (irAEs) that can affect any organ, including the liver. Hepatotoxicity primarily manifests as hepatitis and, less frequently, cholangitis. Several risk factors, such pre-existing autoimmune and liver diseases, type of combination regimens, play a role in hepatotoxicity (irH), although reliable predictive markers or models are still lacking. The severity irH ranges from mild to severe cases, up to, rare instances, acute failure. Management strategies require regular monitoring for early diagnosis interventions, encompassing strict cases permanent suspension forms. Corticosteroids backbone treatment moderate high-grade damage, alone additional immunosuppressive drugs resistant refractory cases. Given relatively low number lack dedicated prospective studies, much uncertainty remains about optimal management irH, especially most This review presents main features focusing on injury patterns mechanisms, provides an overview landscape, standard care latest evidence.

Language: Английский

Targeting Immune Checkpoint Inhibitors for Non-Small-Cell Lung Cancer: Beyond PD-1/PD-L1 Monoclonal Antibodies DOI Open Access
Nicolas Roussot,

Courèche Kaderbhaï,

François Ghiringhelli

et al.

Cancers, Journal Year: 2025, Volume and Issue: 17(5), P. 906 - 906

Published: March 6, 2025

Non-small-cell lung cancer (NSCLC) remains a leading cause of cancer-related mortality worldwide. Immunotherapy targeting the PD-1/PD-L1 axis has revolutionized treatment, providing durable responses in subset patients. However, with fewer than 50% patients achieving significant benefits, there is critical need to expand therapeutic strategies. This review explores emerging targets immune checkpoint inhibition beyond PD-1/PD-L1, including CTLA-4, TIGIT, LAG-3, TIM-3, NKG2A, and CD39/CD73. We highlight biological basis CD8 T cell exhaustion shaping antitumor response. Novel approaches additional inhibitory receptors (IR) are discussed, focus on their distinct mechanisms action combinatory potential existing therapies. Despite advancements, challenges remain overcoming resistance optimizing patient selection. underscores importance dual blockade innovative bispecific antibody engineering maximize outcomes for NSCLC

Language: Английский

Citations

1
Immune Checkpoint Inhibitors: Fundamental Mechanisms, Current Status and Future Directions DOI Creative Commons

Abdullah Younis,

John G. Gribben

Immuno, Journal Year: 2024, Volume and Issue: 4(3), P. 186 - 210

Published: July 5, 2024

Immune checkpoint inhibitors (ICI) are a promising form of immunotherapy that have significantly changed the therapeutic landscape for many advanced cancers. They shown unique clinical benefit against broad range tumour types and strong overall impact on survival in studied patient populations. However, there still limitations holding back this from reaching its full potential as possible curative option cancer patients. A great deal research is being undertaken hope driving advancements area, building better understanding mechanisms behind immune inhibition ultimately developing more effective, safer, wider-reaching agents. Taking into account current literature topic, review aims to explore depth basis use ICIs treatment cancers, evaluate efficacy safety, consider limitations, finally reflect what future holds very immunotherapy.

Language: Английский

Citations

7
Current advancement of immune function paradox of tumour-infiltrating cells and their immunotherapeutic targets: a mini-review DOI

VEENA V. TOM,

A. De la Fuente Hernández José, Sumit Mallick

et al.

Naunyn-Schmiedeberg s Archives of Pharmacology, Journal Year: 2025, Volume and Issue: unknown

Published: March 10, 2025

Language: Английский

Citations

0
Management of metastatic melanoma with combinations including PD-1 inhibitors DOI Creative Commons
Lara Valeska Maul, Egle Ramelyte,

Reinhard Dummer

et al.

Expert Opinion on Biological Therapy, Journal Year: 2025, Volume and Issue: unknown

Published: March 30, 2025

Introduction Melanoma is among the most immunogenic malignancies. The advent of immune checkpoint inhibitors (ICIs) has revolutionized landscape melanoma treatment. Long-term durable cancer control possible in nearly 50% non-resectable, metastatic patients with anti-CTLA4 and anti-PD-1 antibodies.

Language: Английский

Citations

0
Immune checkpoint inhibitors: From friend to foe DOI Creative Commons
Prem Rajak

Toxicology Reports, Journal Year: 2025, Volume and Issue: unknown, P. 102033 - 102033

Published: April 1, 2025

Language: Английский

Citations

0
Multifaceted functions of tissue-resident memory T cells in tumorigenesis and cancer immunotherapy DOI Creative Commons

Eun Suk Seo,

Sung‐Kyu Lee, Young Min Son

et al.

Cancer Immunology Immunotherapy, Journal Year: 2025, Volume and Issue: 74(6)

Published: April 26, 2025

Tissue-resident memory T (TRM) cells are well reported as a strong protective first line of defense against foreign antigens in non-lymphoid tissues. Moreover, TRM have demonstrated critical roles antitumor immunity, contributing to enhanced survival and tumor growth inhibition across various cancer types. However, surprisingly, recent studies suggest that can exhibit paradoxical effects, potentially promoting progression under certain conditions leading adverse outcomes during immune responses. Understanding the complexities cell functions will enable us harness their potential advancing immunotherapy more effectively. Therefore, this review comprehensively investigates dual different contexts, highlighting combating cancers unfavorable exacerbate development. Additionally, we explore implications behaviors for future treatment strategies, emphasizing need further research optimize therapeutic exploitation while mitigating deleterious effects.

Language: Английский

Citations

0
Treatment options for immune‐related adverse events associated with immune checkpoint inhibitors DOI Creative Commons

Yu Hua Chen,

Tamás Kovács, Péter Ferdinandy

et al.

British Journal of Pharmacology, Journal Year: 2024, Volume and Issue: unknown

Published: May 27, 2024

Abstract The immunotherapy revolution with the use of immune checkpoint inhibitors (ICIs) started clinical first ICI, ipilimumab, in 2011. Since then, field ICI therapy has rapidly expanded — FDA approval 10 different drugs so far and their incorporation into therapeutic regimens a range malignancies. While ICIs have shown high anti‐cancer efficacy, they also characteristic side effects, termed immune‐related adverse events (irAEs). These effects hinder potential and, therefore, finding ways to prevent treat them is paramount importance. current protocols manage irAEs follow an empirical route steroid administration more severe cases, withdrawal. However, this approach not optimal many as there are often steroid‐refractory irAEs, for corticosteroid promote tumour progression. This review surveys alternative approaches treatments goal summarizing highlighting best attempts without compromising anti‐tumour immunity allowing rechallenge after resolution irAEs.

Language: Английский

Citations

3
Pan-cancer and single-cell analysis reveal dual roles of lymphocyte activation gene-3 (LAG3) in cancer immunity and prognosis DOI Creative Commons
Yongfeng Wang,

Yanzong Zhao,

Guangming Zhang

et al.

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: Oct. 15, 2024

Lymphocyte activating gene-3 (LAG3) is a distinctive T cell co-receptor that expressed on the surface of lymphocytes. It plays special inhibitory immune checkpoint role due to its unique domain and signaling pattern. Our aim explore correlation between LAG3 in cancers physiological processes related range cancers, as well build LAG3-related immunity prognostic models. By comprehensively using datasets methods from TCGA, GTE-x GEO databases, cBioPortal, HPA, Kaplan-Meier Plotter, Spearman, CellMinerTM, we delved deeper into potential impact cancer development. These include expression differences, Localization tumor subsets, infiltration, matrix gene mutations, DNA methylation, pathways prognosis. Furthermore, explored interactions with different drugs. highly ACC (p < 0.001), BRCA DLBC ESCA GBM HNSC KIRC LGG LUAD 0.01), LUSC PAAD PCPG SKCM STAD TGCT 0.001) THCA 0.05), while lowly COAD LIHC OV PRAD READ UCEC UCS 0.001). High correlates longer overall survival (OS) BLCA (HR = 0.67, p CESC 0.3, 0.71, 0.65, 0.68, 0.57, 0.01). Conversely, 1.85, KIRP 2.81, THYM 8.92, high corresponds shorter OS. Comprehensive results for recurrence-free (RFS) indicate acts protective factor BLCA, CESC, OV, UCEC. Moreover, widely tumor-associated lymphocytes, positively correlating scores stromal scores, significantly present C2 subtype across various tumors. increased infiltration. shows associations MSI, TMB, MMR system, participating multiple including receptor pathway. also demonstrates positive correlations sensitivity eleven Unlike traditional checkpoints, exhibits dual roles clinical prognostication pan-cancers, making it significant predictive factor. In some serves risk factor, indicating adverse outcomes. UCEC, associated patient survival. strong within immunity, inflammatory pathways. Elevated levels are linked not only exhaustion but infiltration polarization towards M1 macrophages.

Language: Английский

Citations

1
Insights for the immunotherapy in malignant melanoma: a new revolution DOI Creative Commons
Jiangying Xuan, Zixu Gao, Chuanyuan Wei

et al.

Clinical Cancer Bulletin, Journal Year: 2024, Volume and Issue: 3(1)

Published: Nov. 4, 2024

Abstract Melanoma is highly malignant and mainly occurs in the skin. was first used immunotherapy due to its high immunogenicity, which changed therapeutic pattern of tumor patients. However, many patients do not benefit from because side effects, resistance low sensitivity anti-tumor responses. Recently, with a deeper understanding development, has emerged as new era. In this review, we elucidate effects on microenvironment (TME) mechanisms involved, well how immune cells exert promoting or immunosuppressive impact immunotherapy. Then mention latest progress checkpoint blockades, such CTLA-4, PD-1/PD-L1, TIM3 LAG3. Biotherapies adoptive therapy, RNA vaccines oncolytic virus are also included. Next, elaborate problems existing data explain current clinical situation. To address these challenges, introduce combination strategies targeted radiotherapy, chemotherapy, biotherapy. Numerous have showed that combined treatment can significantly improve effect melanoma Overall, specific introduction may provide fresh perspectives for scientists investigate targets identify treatments.

Language: Английский

Citations

1
Construction of [89Zr]Zr-Labeled HuL13 for ImmunoPET Imaging of LAG-3 Checkpoint Expression on Tumor-Infiltrating T Cells DOI

Lixin Ding,

Feng Wang,

Zilei Wang

et al.

Molecular Pharmaceutics, Journal Year: 2024, Volume and Issue: unknown

Published: June 28, 2024

Lymphocyte activation gene 3 (LAG-3) has attracted much attention as a potentially valuable immune checkpoint. Individual identification of LAG-3 expression at screening and during treatment could improve the successful implementation anti-LAG-3 therapies. HuL13 is human IgG1 monoclonal antibody that binds to receptor in T cells. Here, we used [

Language: Английский

Citations

0