Interstitial lung diseases with concomitant lung cancer: a data mining approach revealing a complex condition with gender- and immune-associated specific implications DOI Creative Commons
Fabio Massimo Perrotta, Donato Lacedonia, Vito D’Agnano

et al.

Frontiers in Oncology, Journal Year: 2024, Volume and Issue: 14

Published: Dec. 17, 2024

Interstitial lung diseases (ILDs) comprise a family of heterogeneous entities, primarily characterised by chronic scarring the parenchyma. Among ILDs, idiopathic pulmonary fibrosis (IPF) is most common interstitial pneumonitis, associated with progressive functional decline leading to respiratory failure, high symptom burden, and mortality. Notably, incidence cancer (LC) in patients already affected ILDs-mainly IPF-is significantly higher than general population. Moreover, these cases are often neglected deprived active oncologic treatments.

Language: Английский

The role of the immunosuppressive PD-1/PD-L1 checkpoint pathway in the aging process and age-related diseases DOI Creative Commons
Antero Salminen

Journal of Molecular Medicine, Journal Year: 2024, Volume and Issue: 102(6), P. 733 - 750

Published: April 11, 2024

Abstract The accumulation of senescent cells within tissues is a hallmark the aging process. Senescent are also commonly present in many age-related diseases and cancer microenvironment. escape abnormal from immune surveillance indicates that there some defect function cytotoxic cells, e.g., CD8 + T natural killer (NK) cells. Recent studies have revealed expression programmed death-ligand 1 (PD-L1) protein abundantly increased An increase amount PD-L1 protects clearance by PD-1 checkpoint receptor In fact, activation suppresses properties NK promoting state immunosenescence. inhibitory PD-1/PD-L1 pathway acts cooperation with immunosuppressive cells; for example, can enhance differentiation regulatory (Treg), myeloid-derived suppressor (MDSC), M2 macrophages, whereas cytokines secreted stimulate protein. Interestingly, signaling pathways known to promote cellular senescence process crucial stimulators protein, epigenetic regulation, inflammatory mediators, mTOR-related signaling, cGAS-STING pathway, AhR signaling. It seems axis has role thus it promotes tissues. Thus, blockade might be potential anti-aging senolytic therapy. Key messages accumulate during diseases. able Expression markedly increases Age-related stimulates Inhibitory

Language: Английский

Citations

23
Emerging role of immune cells as drivers of pulmonary fibrosis DOI
Steven E. Mutsaers,

Tylah Miles,

Cecilia M. Prêle

et al.

Pharmacology & Therapeutics, Journal Year: 2023, Volume and Issue: 252, P. 108562 - 108562

Published: Nov. 10, 2023

Language: Английский

Citations

23
Immune Checkpoints and the Immunology of Liver Fibrosis DOI Creative Commons
Ioannis Tsomidis, Argyro Voumvouraki, Elias Kouroumalis

et al.

Livers, Journal Year: 2025, Volume and Issue: 5(1), P. 5 - 5

Published: Jan. 27, 2025

Liver fibrosis is a very complicated dynamic process where several immune cells are involved. Both innate and adaptive immunity implicated, their interplay always present. Multi-directional interactions between liver macrophages, hepatic stellate (HSCs), cells, cytokines important for the induction perpetuation of fibrosis. Detailed studies proteomics transcriptomics have produced new evidence role individual in cirrhosis. Most these controlled by various checkpoints whose main function to maintain homeostasis implicated cells. Recent indicates that involved In particular, programmed cell death protein 1 (PD-1), death-ligand (PD-L1), cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) been investigated, particularly after availability checkpoint inhibitors. Their activation leads exhaustion CD4+ve CD8+ve promotion this review, current pathogenesis immunological abnormalities discussed. The recent data on involvement identified as possible targets future interventions.

Language: Английский

Citations

1
Cooperation between inhibitory immune checkpoints of senescent cells with immunosuppressive network to promote immunosenescence and the aging process DOI Creative Commons
Antero Salminen

Ageing Research Reviews, Journal Year: 2025, Volume and Issue: unknown, P. 102694 - 102694

Published: Feb. 1, 2025

Language: Английский

Citations

1
Pharmacological targeting of ECM homeostasis, fibroblast activation, and invasion for the treatment of pulmonary fibrosis DOI
Ioannis Tomos,

Paraskevi Kanellopoulou,

Dimitris Nastos

et al.

Expert Opinion on Therapeutic Targets, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 22, 2025

Introduction Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive interstitial lung disease with dismal prognosis. While the standard-of-care (SOC) drugs approved for IPF represent significant advancement in antifibrotic therapies, they primarily slow progression and have limited overall efficacy many side effects. Consequently, remains condition high unmet medical pharmacological needs.

Language: Английский

Citations

1
PD-1/PD-L1 axis in organ fibrosis DOI Creative Commons
Youliang Zhao,

Yaqian Qu,

Changfu Hao

et al.

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: May 19, 2023

Fibrosis is a pathological tissue repair activity in which many myofibroblasts are activated and extracellular matrix excessively accumulated, leading to the formation of permanent scars finally organ failure. A variety organs, including lung, liver, kidney, heart, skin, can undergo fibrosis under stimulation various exogenous or endogenous pathogenic factors. At present, pathogenesis still not fully elucidated, but it known that immune system plays key role initiation progression fibrosis. Immune checkpoint molecules regulators maintain tolerance homeostasis, among programmed cell death protein 1/programmed ligand 1 (PD-1/PD-L1) axis has attracted much attention. The exciting achievements tumor immunotherapy targeting PD-1/PD-L1 provide new insights into its use as therapeutic target for other diseases. In recent years, been preliminarily explored, further confirming close relationship signaling, regulation, This review discusses structure, expression, function, regulatory mechanism PD-1 PD-L1, summarizes research progress signaling fibrotic

Language: Английский

Citations

21
Expression of PD-1/PD-L1 axis in mediastinal lymph nodes and lung tissue of human and experimental lung fibrosis indicates a potential therapeutic target for idiopathic pulmonary fibrosis DOI Creative Commons
Τheodoros Karampitsakos,

Apostolos Galaris,

Serafeim Chrysikos

et al.

Respiratory Research, Journal Year: 2023, Volume and Issue: 24(1)

Published: Nov. 14, 2023

Mediastinal lymph node enlargement is prevalent in patients with idiopathic pulmonary fibrosis (IPF). Studies investigating whether this phenomenon reflects specific immunologic activation are lacking.Programmed cell death-1 (PD-1)/ programmed death ligand-1 (PD-L1) expression mediastinal nodes and lung tissues was analyzed. PD-1, PD-L1 mRNA measured tracheobronchial of mice following bleomycin-induced injury on day 14. Finally, the effect PD-1 inhibitor, pembrolizumab, investigated.We analyzed thirty-three (n = 33, IPF: n 14, cancer: 10, concomitant IPF 9) two hundred nineteen 219, 123, controls: 96). increased, while decreased, compared to cancer lungs control lungs. Tracheobronchial isolated 14 from bleomycin-treated exhibited increased size higher levels saline-treated animals. Pembrolizumab blunted fibrosis, as indicated by reduction Ashcroft score improvement respiratory mechanics.Mediastinal exhibit differential profiles than those indicating distinct immune-mediated pathways regulating fibrogenesis carcinogenesis. line tissue expression. Lower doses pembrolizumab might exert antifibrotic effects. Clinical trials aiming endotype based profiling accordingly implement targeted therapies such inhibitors greatly anticipated.

Language: Английский

Citations

17
Advancing the Boundaries of Immunotherapy in Lung Adenocarcinoma with Idiopathic Pulmonary Fibrosis by a Biomimetic Proteinoid Enabling Selective Endocytosis DOI Creative Commons
Aimin Jiang, Xiaoqiang Zheng, Siqi Yan

et al.

ACS Nano, Journal Year: 2024, Volume and Issue: unknown

Published: Feb. 6, 2024

The coexistence of lung adenocarcinoma (LUAD) with idiopathic pulmonary fibrosis (IPF), which has been extensively documented as a prominent risk factor for checkpoint inhibitor-related pneumonitis (CIP) in patients undergoing immunotherapy, long considered restricted domain the use immune inhibitors (ICIs). To overcome it, an approach was employed herein to specifically target PD-L1 within cellular interior, surpassing conventional focus solely on cytomembrane, thereby facilitating development ICIs capable distinguishing between LUAD cells and noncancerous based their distinctive endocytic propensities. By exploiting aurophilicity-driven self-assembly binding peptide (PDBP) subsequently encapsulating it erythrocyte membranes (EM), resulting biomimetic protein EMS-PDBP exhibited extraordinary selectivity internalizing cells, effectively targeting cancer while hindering its membrane translocation. treatment not only reactivated antitumor response orthotopic allograft mouse model but also demonstrated favorable safety profile by eliminating any immune-related adverse events (irAEs). Most significantly, successfully safely restored coexistent IPF, thus shattering confines immunotherapy. reported collectively offers potential strategy reactivation limitations immunotherapy coexisting IPF.

Language: Английский

Citations

4
Pulmonary fibrosis: pathogenesis and therapeutic strategies DOI Creative Commons
Jianhai Wang, Kuan Li,

De Hao

et al.

MedComm, Journal Year: 2024, Volume and Issue: 5(10)

Published: Sept. 23, 2024

Abstract Pulmonary fibrosis (PF) is a chronic and progressive lung disease characterized by extensive alterations of cellular fate function excessive accumulation extracellular matrix, leading to tissue scarring impaired respiratory function. Although our understanding its pathogenesis has increased, effective treatments remain scarce, fibrotic progression major cause mortality. Recent research identified various etiological factors, including genetic predispositions, environmental exposures, lifestyle which contribute the onset PF. Nonetheless, precise mechanisms these factors interact drive are not yet fully elucidated. This review thoroughly examines diverse molecular mechanisms, key signaling pathways involved in PF, such as TGF‐β, WNT/β‐catenin, PI3K/Akt/mTOR. It also discusses current therapeutic strategies, antifibrotic agents like pirfenidone nintedanib, explores emerging targeting senescence. Emphasizing need for omni‐target approaches overcome limitations therapies, this integrates recent findings enhance PF development more prevention management ultimately improving patient outcomes.

Language: Английский

Citations

4
Recent advances in PD-L1 siRNA nanocarriers for cancer therapy DOI

Sristi,

Garima Gupta, Mohammed A. S. Abourehab

et al.

International Journal of Biological Macromolecules, Journal Year: 2025, Volume and Issue: unknown, P. 143994 - 143994

Published: May 1, 2025

Language: Английский

Citations

0