J Vis Exp. 2025 Jun 13;(220). doi: 10.3791/68464.

ABSTRACT

Pseudomonas aeruginosa is a major human pathogen, particularly in chronic wound infections and chronic pulmonary infections (especially in patients with cystic fibrosis (CF)). Chronic bacterial infections are refractory to antibiotic treatments and there is an urgent need for in vivo chronic infection models amenable to drug screening to develop efficient therapies. Here, we describe a protocol of infection by a P. aeruginosa clinical isolate from a CF patient, expressing constitutively the Green Fluorescent Protein (GFP), for generating a persistent wound infection in zebrafish larvae. Tail fin-injured embryos are immersed in a bacterial suspension for 1.5 h, washed, and monitored for bacterial load for 3 days. The bacterial burden was quantified daily by counting fluorescent colony-forming units (CFU) from lysed infected larvae, which allowed a persistent infection. Moreover, persistent P. aeruginosa bacteria were refractory to antibiotic treatment. This novel in vivo model of persistent P. aeruginosa infection offers opportunities to evaluate the efficacy of innovative treatments against chronic infections.

PMID:40587407 | DOI:10.3791/68464

Ann Am Thorac Soc. 2025 Jun 30. doi: 10.1513/AnnalsATS.202411-1151OC. Online ahead of print.

ABSTRACT

In cystic fibrosis (CF), body composition alterations are observed. Prevalence of obesity in CF is increasing with evidence suggesting a subsequent increase in cardiometabolic risk. We sought to assess body composition using analytic morphomics (AM) from ultra-low dose thoracic CT scans in CF patients on the triple CFTR modulator therapy, Elexacaftor/Tezacaftor/Ivacaftor (ETI). Objective Our objective was to use analytical morphomics on routine ultra-low dose CTs to assess patterns of change in body composition in CF patients on ETI therapy. Methods Forty-two CF patients on ETI who had baseline and follow up ultra-low dose thoracic CT imaging were retrospectively analysed. The CTs were acquired at a radiation dose equivalent to 2 frontal chest x-rays using our previously published acquisition parameters. The Bhalla score was used as a marker of structural lung disease severity. AM variables including: cross sectional area (CSA) and attenuation of pectoralis muscle, visceral fat (epicardial and upper abdominal) and subcutaneous fat were extracted using the validated image segmentation software, CoreSlicer. Paired samples mean testing (Wilcoxon matched pairs signed rank test) and Spearman rank correlation analyses were performed. Results Total Bhalla scores significantly improved over time in patients on ETI (p < 0.0001). In addition, body composition also changed with an increase in the CSA of subcutaneous, and epicardial visceral fat (p values < 0.0001, and 0.0062, respectively). In those with a normal BMI at follow up, epicardial, and subcutaneous fat had also increased significantly in the interval (p = 0.0066, and 0.0002, respectively). Conclusion In CF, ETI produced a significant improvement in structural lung disease over time, however also resulted in an increase in visceral and subcutaneous fat. The AM methodology presented herein, may help identify those patients for aggressive primary prevention strategies and permit the creation of more personalised nutritional plans.

PMID:40587244 | DOI:10.1513/AnnalsATS.202411-1151OC

Rhinology. 2025 Jun 30. doi: 10.4193/Rhin24.568. Online ahead of print.

ABSTRACT

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a relatively uncommon condition in the paediatric population, with a prevalence estimated at 0.1-0.8%, compared to approximately 4% in adults (1, 2). The early onset of CRSwNP emphasises the significant role of genetic factors in its pathophysiology (3). Approximately 20% of paediatric patients with CRSwNP are associated with systemic genetic disorders, with cystic fibrosis (CF) being the most prevalent (2). CF is characterised by a dysfunction of the CF transmembrane conductance regulator (CFTR) protein. Over 2,000 distinct CFTR variants have been identified, resulting in varying organ involvement and disease severity. In 2000, the World Health Organization introduced the term "CFTR-related disorders" (CFTR-RDs) to include clinical entities associated with CFTR dysfunction that do not meet the diagnostic criteria for CF (4). CFTR-RDs include congenital bilateral absence of the vas deferens (CBAVD), recurrent pancreatitis (RP), and disseminated bronchiectasis (DB). However, recent studies emphasised a significant prevalence of heterozygous CFTR pathogenic variants in paediatric and adult CRSwNP populations without CF (4-8). We assessed the prevalence of CFTR variants in a paediatric population with CRSwNP.

PMID:40586793 | DOI:10.4193/Rhin24.568

Aesthet Surg J. 2025 Jun 28:sjaf128. doi: 10.1093/asj/sjaf128. Online ahead of print.

ABSTRACT

BACKGROUND: The Australian Breast Device Registry (ABDR) records breast implant surgeries Australia-wide. In addition to clinical data, the ABDR has collected Patient Reported Outcome Measures (PROMs), to better understand patient outcomes following implant surgery.

OBJECTIVES: Our objective was to assess the association between postoperative PROMs and revision surgery due to complications for reconstructive and cosmetic breast implant patients.

METHODS: A cohort study design was used. All primary breast augmentation and breast reconstruction implant insertion procedures with 2-years of follow-up after PROMs response, and with at least one PROM completed between 30th October 2017 and 16th May 2021 registered with the ABDR were identified. The primary outcome investigated was complications requiring revision at 2-years post PROMs completion. Binary logistic regression models were used to assess the predictive ability of PROMs.

RESULTS: 5321 reconstructive procedures, and 25,777 cosmetic breast procedures were followed. Multivariate regression for the reconstructive cohort showed 3 PROM variables, feel, rippling and tightness, predicted revision due to complications within 2-years of PROMs response, OR 0.71, 95% CI 0.56-0.90; p equals 0.004, OR 0.70, 95% CI 0.57-0.87; p less than 0.001, and OR 0.80, 95% CI 0.69-0.93; p equals 0.003 respectively. Multivariate regression for the cosmetic cohort showed 3 PROM variables, look, rippling and tightness, predicted revision due to complications within 2-years of PROMs response, OR 0.51, CI 0.42-0.63; p less than 0.001, OR 0.78, CI 0.63-0.95; p equals 0.014, and OR 0.79, CI 0.67-0.94; p equals 0.006 respectively.

CONCLUSIONS: Postoperative PROMs were significantly associated with revision surgery due to complications. PROMs may be used to predict the likelihood of complications and revision following breast implant surgery.

PMID:40580493 | DOI:10.1093/asj/sjaf128

Pediatr Blood Cancer. 2025 Jun 28:e31887. doi: 10.1002/pbc.31887. Online ahead of print.

NO ABSTRACT

PMID:40580014 | DOI:10.1002/pbc.31887

J Int Med Res. 2025 Jun;53(6):3000605251352789. doi: 10.1177/03000605251352789. Epub 2025 Jun 28.

ABSTRACT

Neutrophil elastase is a serine protease secreted by neutrophils that plays a crucial role in the onset and progression of various respiratory diseases. The imbalance between neutrophil elastase and its endogenous inhibitors can contribute to the onset and progression of respiratory diseases such as chronic obstructive pulmonary disease, cystic fibrosis, bronchiectasis, and acute respiratory distress syndrome. The excessive release of neutrophil elastase contributes to multiple pathophysiological processes, such as disruption of the alveolar-capillary barrier, oxidative stress and inflammatory responses, autophagy, and apoptosis. The use of neutrophil elastase as a biomarker in disease assessment and prognosis prediction as well as the potential of neutrophil elastase inhibitors in clinical treatment have shown broad application prospects. Neutrophil elastase inhibitors have certain limitations such as off-target effects, poor lung bioavailability, cost considerations, and variability in patient responses. This article reviews the literature on neutrophil elastase and its inhibitors in the field of respiratory diseases, aiming to provide new insights into the diagnosis and treatment of related respiratory diseases.

PMID:40579944 | DOI:10.1177/03000605251352789

Disabil Rehabil. 2025 Jun 28:1-6. doi: 10.1080/09638288.2025.2523975. Online ahead of print.

ABSTRACT

PURPOSE: To investigate the validity and reliability of the Turkish version of the Bronchiectasis Health Questionnaire (BHQ) in individuals with bronchiectasis.

METHODS: Ninety-four individuals with stable non-cystic fibrosis bronchiectasis were included. Physical characteristics and spirometric parameters were recorded. The Turkish version of the BHQ was formed and used to assess disease-specific quality of life. The St. George's Respiratory Questionnaire (SGRQ) was used to evaluate quality of life. Dyspnea at rest and on effort was assessed using the modified Borg scale (mBorg). The presence of daily cough and daily sputum expectoration was questioned.

RESULTS: Cronbach's alpha coefficient of the Turkish version of the BHQ was 0.796 with a McDonald's Omega of 0.801. The ICC value of 0.934 indicated excellent reliability. The BHQ score was negatively correlated with the SGRQ-total (r = -0.762, p < 0.001), SGRQ-symptom (r = -0.657, p < 0.001), SGRQ-activity (r = -0.635, p < 0.001), SGRQ-impact (r = -0.732, p < 0.001), and mBorg scores (r = -0.401, p = 0.001). The participants with dyspnea at rest and on effort, daily cough, and daily sputum expectoration had lower BHQ scores than those without these complaints (p < 0.001, p = 0.034, p = 0.009, and p = 0.007, respectively).

CONCLUSIONS: The Turkish version of the BHQ has an acceptable validity and excellent reliability, enabling a disease-specific quality of life measurement in bronchiectasis.

PMID:40579923 | DOI:10.1080/09638288.2025.2523975

BMJ Case Rep. 2025 Jun 27;18(6):e264906. doi: 10.1136/bcr-2025-264906.

ABSTRACT

A man in his 60s, under dual immunosuppression following bilateral lung transplantation (BiLuTx), developed bacteraemia and septic shock by Pseudomonas aeruginosa with ecthyma gangrenosum. Symptoms emerged acutely a few weeks after he had received high-dose intravenous steroid treatment for acute cellular graft rejection (ACR). The suspected route of entry of the pathogen was a minor accidental skin injury. Despite the severity of his condition, he successfully recovered after an intensive 26-day course of intravenous antibiotic therapy.

PMID:40579190 | DOI:10.1136/bcr-2025-264906

Biochem Biophys Res Commun. 2025 Jun 24;777:152251. doi: 10.1016/j.bbrc.2025.152251. Online ahead of print.

ABSTRACT

Chronic exposure to environmental pathogens and pollutants can impair CFTR chloride channel function, contributing to chronic obstructive pulmonary disease (COPD). Our previous study demonstrated that pyocyanin (PYO), a COPD-associated pathogen factor, significantly reduces the functional expression of R75Q- or M470V-CFTR, two CFTR polymorphisms found in COPD patients, leading to increased IL-8 production in airway epithelial cells (AEC). In this study, we report that inhibition of RFFL, a ubiquitin ligase that targets CFTR mutants for removal from the plasma membrane (PM), mitigates excessive IL-8 production in AECs expressing R75Q- or M470V-CFTR, even in the presence of PYO. RFFL knockdown (KD) enhanced the functional PM expression of R75Q- or M470V-CFTR under PYO exposure, although it did not prevent PYO-induced CFTR downregulation. Our results indicate that RFFL likely regulates constitutive IL-8 production independently of CFTR, while also modulating pathogen-induced IL-8 expression through a CFTR-dependent mechanism. This highlights the potential of RFFL inhibitors to enhance CFTR function and reduce IL-8 secretion, even amid chronic exposure to environmental pathogens and pollutants, underscoring RFFL inhibition as a promising therapeutic approach for COPD management.

PMID:40578289 | DOI:10.1016/j.bbrc.2025.152251

Indian J Pediatr. 2025 Jun 27. doi: 10.1007/s12098-025-05620-9. Online ahead of print.

NO ABSTRACT

PMID:40576730 | DOI:10.1007/s12098-025-05620-9

Clin Pediatr (Phila). 2025 Jun 27:99228251351699. doi: 10.1177/00099228251351699. Online ahead of print.

ABSTRACT

BACKGROUND: Pseudomonas aeruginosa (PA) eradication is crucial in cystic fibrosis (CF) management. At our center, the success rate was 21.6%, prompting a revised eradication protocol to evaluate a new regimen.

METHODS: Cystic fibrosis patients with first-time PA detection were included. Nonmucoid PA cases received oral ciprofloxacin (3 weeks) and inhaled tobramycin (1 month). For mucoid PA or failed eradication, ciprofloxacin (3 weeks) and extended nebulized therapy (3 months, alternating tobramycin/colistin) were used. Intravenous antibiotics were given to unwell patients.

RESULTS: Among 109 CF patients (median age: 6 years), 79 (72.5%) achieved successful eradication. Oral ciprofloxacin and tobramycin inhalation were used in 66 patients (60.6%), extended nebulized therapy in 26 (23.8%), and intravenous antibiotics in 17(15.6%).

CONCLUSION: The revised protocol achieved a high PA eradication rate in CF patients. Adapting treatment regimens based on PA characteristics and patient condition can optimize outcomes and improve CF management.

PMID:40576045 | DOI:10.1177/00099228251351699

Pharmaceutics. 2025 May 30;17(6):725. doi: 10.3390/pharmaceutics17060725.

ABSTRACT

Background/Objectives: Filamentous fungi, in particular the species Aspergillus, Scedosporium, and Exophiala, frequently colonize the lungs of cystic fibrosis (CF) patients. Chronic colonization is linked to hypersensitivity reactions and persistent infections leading to a significant long-term decline in lung function. Azole antifungal therapy such as voriconazole (VRC) slows disease progression, particularly in patients with advanced CF; however, excessive mucus production in CF lungs poses a diffusional barrier to effective treatment. Methods: Here, biodegradable nanohydrogels (NHGs) recently developed as nanocarriers were evaluated for formulating VRC as a platform for treating fungal infections in CF lungs. The NHGs entrapped up to about 30 μg/mg of VRC, and physicochemical properties were investigated via dynamic laser light scattering and nanoparticle tracking analysis. Diameters were 100-400 nm, and excellent colloidal stability was demonstrated in interstitial fluids, indicating potential for pulmonary delivery. Nano-formulations exhibited high in vitro cytocompatibility in A549 and HEK293T cells and were tested for the release of VRC under two different sink conditions. Results: Notably, the antifungal activity of VRC-loaded nanohydrogels was up to eight-fold greater than an aqueous suspension drug against different fungal species isolated from CF sputum, regardless of the presence of a CF artificial mucus layer. Conclusions: These findings support the development of potent VRC nano-formulations for treating fungal disorders in CF lungs.

PMID:40574038 | DOI:10.3390/pharmaceutics17060725

Vaccines (Basel). 2025 Jun 7;13(6):619. doi: 10.3390/vaccines13060619.

ABSTRACT

Background: The prevalence of pulmonary nontuberculous mycobacteria (NTM) is increasing in Europe and North America. Most pulmonary NTM cases are caused by Mycobacterium avium complex (MAC). The treatment of pulmonary MAC is suboptimal with failure rates ranging from 30% to 40% and there is a need to develop new vaccines. Methods: We tested the ability of two whole-cell vaccines, DAR-901 (heat-killed M. obuense) and BCG (live-attenuated M. bovis), to induce MAC cross-reactive immunity by first immunizing BALB/c mice and then performing IFN-γ ELISPOT assays after overnight stimulation of splenocytes with live MAC. To study the ability of these vaccines to protect against MAC infection, BALB/c mice were vaccinated with DAR-901 (intradermal) or BCG (subcutaneous or intranasal) and challenged with aerosolized MAC 4 weeks later. A group of mice vaccinated with BCG were also treated with clarithromycin via gavage. Lung colony-forming units (CFU) in immunized mice and unvaccinated controls were quantified 4 weeks after infection. Histopathology was used to quantify lung inflammation and flow cytometry was used to study lung immunity in BCG-vaccinated and unvaccinated mice following MAC infection. To increase the safety profile of mucosal BCG vaccination, we studied BCG with a "kill switch" (tetR BCG) in scnn1b-transgenic mice (i.e., mice prone to cystic fibrosis-type lung diseases). Results: Our results showed that (i) DAR-901 induced cross-reactive immunity to MAC to a similar level as BCG, (ii) DAR-901 and BCG protected against aerosol MAC challenge, (iii) mucosal BCG vaccination, compared to systemic BCG and DAR-901 vaccinations, provided the best protection against MAC challenge, (iv) BCG vaccination did not interfere with anti-MAC activities of clarithromycin, (v) BCG-vaccinated mice had increased inflammation and increased frequencies of activated CD4 and CD8 T cells following MAC infection, and (vi) doxycycline treatment of tetR BCG-vaccinated mice decreased lung BCG CFU without affecting MAC immunity. Conclusions: Both DAR-901 and BCG vaccinations induce MAC cross-reactive immunity and protect against aerosolized MAC challenges. Mucosal BCG vaccination provides the best protection and TetR BCG could enhance the safety of mucosal BCG vaccination.

PMID:40573950 | DOI:10.3390/vaccines13060619

Viruses. 2025 Jun 6;17(6):821. doi: 10.3390/v17060821.

ABSTRACT

Therapeutic gene editing strategies utilize endogenous DNA repair pathways-nonhomologous end joining (NHEJ) or homology-directed repair (HDR)-to introduce targeted genomic modifications. Because HDR is restricted to dividing cells, whereas NHEJ functions in both dividing and non-dividing cells, NHEJ-based approaches are better suited for in vivo gene editing in the largely post-mitotic airway epithelium. Homology-independent targeted insertion (HITI), an NHEJ-based method, offers a promising strategy for cystic fibrosis (CF) gene therapy. Here, we applied HITI to drive the expression of a promoterless reporter through an exon trap strategy in both proliferating airway basal cells and well-differentiated primary airway epithelial cultures derived from transgenic ROSAmTmG ferrets. We also established a versatile human gene editing reporter (GER) airway basal cell line capable of multipotent differentiation, enabling real-time visualization of editing outcomes and the quantitative assessment of HDR- and NHEJ-based editing efficiencies. Together, these platforms provide easily accessible tools for optimizing genome editing strategies in the respiratory epithelium and advancing clinically relevant delivery strategies for CF gene therapy.

PMID:40573412 | DOI:10.3390/v17060821

Pharmaceuticals (Basel). 2025 May 24;18(6):784. doi: 10.3390/ph18060784.

ABSTRACT

Cystic fibrosis (CF), a severe genetic disorder stemming from mutations in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene, is characterized by a complex interplay of chronic inflammation and heightened oxidative stress, resulting in substantial patient morbidity. The diverse array of CFTR mutations, categorized into seven distinct classes based on their functional impact on the CFTR protein, presents a significant obstacle to effective therapeutic intervention. While CFTR modulator therapies offer clinical benefits, their applicability is restricted to specific mutation classes, leaving a considerable portion of the CF patient population with unmet therapeutic needs. This review provides a critical analysis of the intricate role of oxidative stress in CF, meticulously examining its origins, mechanistic pathways and downstream pathological consequences, with particular emphasis on lipid peroxidation (LPO). It elucidates the nuanced connection between LPO and inflammatory processes driven by cellular stressors such as endoplasmic reticulum dysfunction, mitochondrial impairment and persistent bacterial infections. Furthermore, it evaluates the current landscape of therapeutic proposals targeting oxidative stress, including antioxidant interventions, and explores the potential of microRNAs (miRNAs) as novel targets. This review aims to synthesize existing research to provide a comprehensive understanding of oxidative stress involvement in CF pathogenesis while critically appraising the advantages and limitations of current antioxidant therapeutic strategies.

PMID:40573184 | DOI:10.3390/ph18060784

Medicina (Kaunas). 2025 Jun 7;61(6):1055. doi: 10.3390/medicina61061055.

ABSTRACT

Background and Objectives: Chronic respiratory diseases, such as COPD, cystic fibrosis, and post-COVID-19, are frequently accompanied by psychological distress and physical impairment. As a non-pharmacological intervention, progressive muscle relaxation (PMR) may benefit these patients psychologically and physiologically. This systematic review aimed to evaluate the effects of PMR on anxiety, depression, fatigue, sleep quality, dyspnea, and pulmonary function in patients with COPD, CF, and COVID-19. Materials and Methods: Following PRISMA guidelines, a comprehensive search was conducted across PubMed, Scopus, Web of Science, MEDLINE, Cochrane, SpringerLink, and ClinicalTrials.gov. Eligible studies assessed PMR in adult patients with COPD, CF, or COVID-19. Psychological and physical outcomes were extracted, and methodological quality and risk of bias were evaluated using standardized tools. Results: A total of 32 studies were included in the analysis. PMR was consistently associated with reductions in anxiety, depression, fatigue, and sleep-related distress, particularly in patients with COPD and COVID-19. Some also reported improvements in dyspnea and mild pulmonary function tests, but these were more variable. Only one study evaluated PMR in patients with cystic fibrosis, providing the first clinical data for this group. Interventions were predominantly short-term, with significant variation in design, duration, and methodology, and the risk of bias was often moderate or high. Conclusions: PMR is a helpful strategy in treating chronic respiratory diseases, particularly for reducing psychological distress and improving sleep. However, the evidence is limited by methodological variations and lack of long-term follow-up. Rigorous research is needed to support clinical application, particularly in cystic fibrosis.

PMID:40572743 | DOI:10.3390/medicina61061055

FEBS Lett. 2025 Jun 26. doi: 10.1002/1873-3468.70101. Online ahead of print.

ABSTRACT

Cystic fibrosis (CF) is a recessive disorder caused by mutations in the gene encoding cystic fibrosis transmembrane conductance regulator (CFTR), a chloride/bicarbonate channel that balances fluid homeostasis in epithelia. CFTR dysfunction results in chronic lung infections, pancreatic insufficiency, and salty sweat. Since the discovery of the CFTR gene in 1989, a unique scientific community in both academia and industry has significantly increased our understanding of CF mechanisms. Such knowledge led to spectacular advancements in treatment, from symptom management to CFTR modulators (CFTRm) that alter the mutant protein properties in a mutation-specific way, significantly improving life quality and expectancy of people with CF (pwCF). Emerging genotype-agnostic approaches, such as gene/mRNA therapy, hold promise for future curative treatments for all pwCF. In parallel, precision medicine is revolutionizing CF care through patient-specific therapies, namely for pwCF with genotypes not eligible for CFTRm. However, challenges remain, including high treatment costs, accessibility issues, variable patient responses, and, importantly, the high cancer propensity in pwCF. CF is a model for translational medicine, highlighting the relevance of fundamental research. Insights gained from CF research may also inform therapeutic advancements for other (genetic) diseases.

PMID:40571992 | DOI:10.1002/1873-3468.70101

Pediatr Pulmonol. 2025 Jun;60(6):e71177. doi: 10.1002/ppul.71177.

ABSTRACT

BACKGROUND: Food insecurity is increasing in prevalence throughout the general population and has been noted to substantially exist within the cystic fibrosis (CF) community as well. Nutritional grant programs are in place to provide additional support to people with cystic fibrosis (PwCF). This study was designed to determine the current usage rate of nutritional grant funding as well as clinical outcomes such as body mass index (BMI). We aim to describe our CF center's enrollment and usage of privately funded nutritional grants and explore potential correlations to nutrition clinical outcomes.

METHODS: A single center retrospective chart review of the electronic health records (EHR) to collect requested data points was completed for all PwCF seen at that center between the dates of March 1, 2017 and February 29, 2024.

RESULTS: Two hundred and nineteen individuals met inclusion criteria. Over the course of the study period, the total number of PwCF enrolled in supplemental nutritional grant program(s) and amount of grant utilization increased steadily from 9% enrolled with 17% utilization in 2017 to 27% enrolled with 44% utilization in 2022, respectively. The percentage of PwCF with a BMI below Cystic Fibrosis Foundation (CFF) recommended goals also decreased over the course of the study period from 39% in 2017 to 31% in 2022.

CONCLUSIONS: We conclude that the results of our study support continued efforts to identify and remediate the presence of food insecurity within the CF community.

PMID:40571964 | DOI:10.1002/ppul.71177

Pediatr Pulmonol. 2025 Jun;60(6):e71181. doi: 10.1002/ppul.71181.

NO ABSTRACT

PMID:40571963 | DOI:10.1002/ppul.71181

Nat Rev Drug Discov. 2025 Jun 26. doi: 10.1038/s41573-025-01227-z. Online ahead of print.

ABSTRACT

The depletion or accumulation of metabolites in the tumour microenvironment is one of the hallmarks of cancer, but targeting cancer cell metabolism therapeutically must also take into account the impact on metabolic pathways in immune cells. As we understand more about immunometabolism, opportunities arise for synergies between agents that modulate metabolism and immunotherapy. In this Review, we discuss the pivotal role of metabolic pathways in both cancer and immune cells in shaping the tumour microenvironment. We survey major anabolic and catabolic pathways and discuss how metabolic modulators and dietary nutrients can improve the anticancer immune response and overcome drug resistance mechanisms. Agents in the clinic include inhibitors of the adenosine and tryptophan pathways, and we discuss opportunities and challenges for successful drug development in the context of immune checkpoint blockade and chimeric antigen receptor (CAR)-T cell therapies.

PMID:40571788 | DOI:10.1038/s41573-025-01227-z