Search Results (481)

Microplastics are emerging environmental contaminants capable of crossing epithelial barriers and circulating systemically, potentially affecting organisms, including humans. This study investigated the hematological and biochemical effects of sub-chronic oral exposure to polystyrene microplastics (PS-MPs) in male Swiss albino mice. Animals received 1 μm PS-MPs in drinking water at 0.01 mg/day for four weeks, followed by a two-week recovery period. Blood samples were collected weekly for hematological and biochemical analysis. PS-MP exposure resulted in an increased number of certain immunocytes after the first week of treatment. The highest values compared with the control group were observed in Week 2, reaching 18.5 ± 4.61 vs. 7.2 ± 1.14; 10.9 ± 2.58 vs. 5.1 ± 1.20; and 5.8 ± 2.35 vs. 2.2 ± 0.69 × 10⁹ cells/L for white blood cells, lymphocytes, and granulocytes, respectively (p < 0.001). A significant increase in platelet count was also observed, becoming evident by Week 6 (725.8 ± 307.96 vs. 470.1 ± 121.87 × 10⁹ cells/L, p < 0.05). The elevated alanine aminotransferase and aspartate aminotransferase activities observed after PS-MP exposure were potentially associated with hepatic pathology, erythrocyte damage, and inflammatory responses. No significant recovery was observed during the period after exposure. These findings demonstrate that sub-chronic oral PS-MP exposure induces inflammatory responses and may disrupt organ function. Full article

Pregnancy represents a dynamic immunological state in which the maternal immune system must balance tolerance toward the semi-allogeneic fetus while maintaining antimicrobial defense. Cytomegalovirus (CMV) infection is highly prevalent worldwide and profoundly shapes immune cell differentiation and long-term activation in adults. However, its interaction with pregnancy-associated immune remodeling remains incompletely defined. In this prospective longitudinal study, we comprehensively analyzed immune profiles of healthy pregnant women across all three trimesters and age-matched nonpregnant controls, stratified by CMV IgG serostatus. Multiparametric flow cytometry characterized T and B cell subsets and cytokine production following in vitro stimulation, while circulating cytokines and adhesion molecules were quantified using multiplex immunoassay. Gestational age was the primary determinant of leukocyte dynamics. Nevertheless, CMV-seropositive pregnant women showed enhanced activation and differentiation of CD4⁺ and, more prominently, CD8⁺ T cell subsets, changes not observed in nonpregnant women. Despite pronounced cellular differences, serum cytokine and adhesion molecule levels were largely comparable between CMV-seropositive and CMV-seronegative participants in both pregnant and nonpregnant groups. Functionally, CMV-seropositive women exhibited enrichment of IFN-γ– and IL-21–producing T cells, whereas B cell responses remained predominantly IL-10–dominated. These findings indicate selective alterations in maternal lymphocyte activation and function during pregnancy in CMV-seropositive women, without evidence of systemic inflammation. Full article

Plaque psoriasis (PP) is a chronic immune-mediated skin disorder characterized by T-cell dysregulation and an imbalance between regulatory T cells (Treg) and T helper 17 (Th17) cells. Cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), a key inhibitory checkpoint molecule expressed on Treg cells, and its soluble isoform (sCTLA-4) are critical regulators of peripheral immune tolerance and may contribute to PP pathogenesis. This case–control study evaluated the association between the +49 A>G variant of the CTLA4 gene (rs231775) and susceptibility to PP in a mestizo population from western Mexico and assessed serum sCTLA-4 levels. A total of 204 patients with PP and 214 control subjects (CS) were genotyped using PCR-RFLP, and sCTLA-4 concentrations were measured by ELISA. The AG genotype was the most frequent in both groups (49% in PP and 53% in CS), with no significant differences in genotype or allele distributions. Serum sCTLA-4 levels were significantly higher in CS compared to patients (p < 0.05), and no genotype-dependent differences were observed. The rs231775 variant was not associated with PP susceptibility in this population. However, reduced circulating sCTLA-4 levels in patients suggest impaired CTLA-4-mediated immune regulation independent of this variant. Full article

Dang Gui (Radix Angelica sinensis), a classic Chinese medicinal herb, is renowned for nourishing blood, promoting blood circulation, regulating meridians, and relieving pain, and widely used clinically for anemia, cancer, rheumatoid arthritis, ulcerative colitis, and other diseases. Studies have confirmed that Dang Gui and its major bioactive components (e.g., polysaccharides, ferulic acid, (Z)-ligustilide) exert diverse pharmacological activities including immunomodulation, neuroprotection, and hepatoprotection. Based on a systematic literature search, this review summarizes the traditional applications and main chemical constituents of A. sinensis, with a focused analysis of its immunomodulatory effects. Evidence shows that A. sinensis exerts bidirectional immunoregulation by improving immune organ indices, promoting the proliferation and activation of immune cells, including T/B lymphocytes (T/B cells), macrophages, and regulating cytokine secretion. Furthermore, it reviews its immunomodulatory mechanisms in immune-related diseases (e.g., cancer, aplastic anemia, chronic pain), analyzes its quality control standards from regulatory and pharmacopeial perspectives and summarizes relevant safety research. This review comprehensively integrates the immunoregulatory effects and underlying mechanisms of A. sinensis, aiming to provide a scientific basis for its future research and clinical application. Full article

Background/Objectives: Psoriatic disease is a systemic inflammatory condition associated with increased cardiometabolic risk, but the impact of contemporary systemic therapies and narrowband ultraviolet B (NB-UVB) phototherapy on vascular and systemic inflammatory markers remains incompletely characterized. We aimed to systematically synthesize prospective evidence on treatment-associated changes in vascular inflammation and systemic inflammatory biomarkers in adults with moderate-to-severe psoriatic disease. Specifically, we evaluated changes assessed by 18F-FDG PET/CT imaging and circulating biomarkers following biologic therapies or NB-UVB phototherapy. Methods: We systematically searched MEDLINE, Embase, Web of Science, Scopus, and CENTRAL from inception to 31 January 2026 for prospective interventional and observational studies in adults with psoriasis or psoriatic arthritis treated with biologic agents targeting TNF-α, IL-12/23, IL-17, or IL-23, or with NB-UVB phototherapy. Eligible studies were required to report serial assessments of vascular inflammation by 18F-FDG PET/CT (typically aortic target-to-background ratio) and/or systemic inflammatory markers (high-sensitivity C-reactive protein, interleukin-6, TNF-α, GlycA, or hematologic indices such as the neutrophil-to-lymphocyte ratio) over at least 8 weeks of follow-up. We imposed no language restrictions and included only full-text, peer-reviewed prospective studies. Risk of bias was evaluated using RoB 2 for randomized trials and ROBINS-I for nonrandomized studies. Random-effects meta-analyses were prespecified for outcomes reported by at least two clinically comparable studies; however, because of substantial heterogeneity in reporting and methodology, effect estimates were summarized using a structured narrative synthesis. Results: Thirteen prospective studies (n ≈ 900 adults, published 2015–2025) met inclusion criteria, including four studies with serial 18F-FDG PET/CT imaging and one additional PET/CT study providing baseline observational data on vascular inflammation, as well as eight biomarker-focused prospective cohorts. Across randomized mechanistic trials and observational studies, biologic therapies reduced aortic target-to-background ratio by approximately 6–12% over 12–24 weeks (e.g., mean change from 2.42 to 2.18 with TNF-α inhibition and from 2.51 to 2.20 with IL-17 blockade), and no study reported worsening of PET-derived vascular indices under effective systemic treatment. Biologic and other systemic therapies produced concordant reductions in hs-CRP (typically by 30–50%), IL-6, TNF-α, GlycA, and blood-count-derived indices including neutrophil-to-lymphocyte ratio, with biomarker improvements frequently paralleling reductions in cutaneous disease activity and cardiometabolic risk markers. Two NB-UVB cohorts demonstrated significant hs-CRP reductions of roughly 20–30% and modulation of vitamin D-related inflammatory proteins, suggesting systemic anti-inflammatory effects, although these changes appeared less pronounced than with biologic therapy and were not accompanied by vascular imaging. Conclusions: Contemporary systemic psoriasis therapies, particularly biologic agents targeting the IL-23/Th17 axis and TNF-α, are associated with consistent reductions in aortic vascular inflammation and broad improvements in systemic inflammatory biomarkers, whereas NB-UVB phototherapy confers more modest but measurable systemic anti-inflammatory effects, although the current evidence does not allow differentiation between individual biologic classes in terms of magnitude of effect. Although reductions in vascular and systemic inflammatory markers were observed across therapies targeting TNF-α, IL-12/23, IL-17, and IL-23, the small number of mechanistic imaging studies and absence of head-to-head comparisons do not allow robust differentiation between biologic classes or support a uniform class effect. The convergence of imaging and biomarker data reinforces psoriasis as a clinically relevant model of inflammation-driven atherosclerosis and supports the concept that effective control of psoriatic inflammation may contribute to cardiovascular risk modification, highlighting the need for integrated cardiovascular risk assessment in routine care. However, the imaging evidence base remains limited to four small mechanistic PET/CT studies with relatively short follow-up, which constrains the strength and generalizability of conclusions regarding vascular inflammation. Larger, adequately powered, event-driven prospective trials with standardized imaging and biomarker endpoints are needed to determine whether these vascular and systemic anti-inflammatory effects translate into reduced cardiovascular events in psoriatic disease; because of methodological and reporting heterogeneity across the 13 included studies, these conclusions are based on a structured narrative synthesis rather than a formal quantitative meta-analysis. PROSPERO registration number: CRD420261296646. Full article

Vitamin D is a pleiotropic secosteroid with endocrine and intracrine actions that influence key phases of allogeneic hematopoietic stem cell transplantation. Epithelial barriers, antigen-presenting cells and effector lymphocytes express the vitamin D receptor and enzymes required for local activation, allowing circulating 25-hydroxyvitamin D to be converted into its active form and modulate immune interactions. During the peri-transplant period, sunlight deprivation, reduced intake, mucosal injury, cholestasis and corticosteroid exposure markedly reduce vitamin D levels at a time when antigen presentation and immune reconstitution occur. This review integrates mechanistic immunology with clinical observations and interventional data to outline strategies that prevent severe deficiency. It summarizes epidemiology before and after transplantation, associations with acute and chronic graft-versus-host disease, relapse, engraftment, infections, bone health and survival, and evaluates dosing approaches including pre-conditioning loading and reassessment at day thirty with escalation if needed. Absorption-savvy formulations such as oral thin-film and intramuscular cholecalciferol are considered when gastrointestinal function is compromised. Given the high prevalence of deficiency, biological plausibility, safety and low cost, a structured approach that includes screening, repletion and monitoring to achieve concentrations of at least thirty nanograms per milliliter by day thirty represents a pragmatic and low-risk component of supportive care pending definitive evidence. Full article

Pulmonary arterial hypertension (PAH) has traditionally been viewed as a vasculocentric disorder, with current therapies failing to reverse vascular remodeling or address pervasive systemic metabolic abnormalities. This review synthesizes emerging evidence to propose a paradigm shift, conceptualizing PAH as a systemic metabolic–immunological network disease. It examines how metabolic dysfunction in peripheral organs (adipose tissue, liver, skeletal muscle) and immunometabolic reprogramming of immune cells (e.g., macrophages, lymphocytes) synergistically drive pathology. These components engage in dynamic crosstalk via circulating mediators (metabolites, adipokines, cytokines), creating a self-amplifying loop that fuel pulmonary vascular inflammation and remodeling. Key mechanisms explored include adipose tissue endocrine dysfunction (contributing to the obesity paradox), hepatic insulin resistance and bile acid signaling, skeletal muscle energy crisis and wasting, and the pivotal roles of macrophage glycolytic polarization and T-cell subset imbalance. Insulin resistance/hyperglycemia emerges as a central hub linking metabolic and immune dysregulation. The review concludes that future therapeutic strategies must move beyond vasodilation to target this systemic network, discussing the potential of repurposed metabolic agents, direct immunometabolic modulators, and integrated lifestyle interventions to disrupt disease progression. Full article

Background/Objectives: Coronary collateral circulation (CCC) reduces ischemic damage in patients with chronic total occlusion (CTO), yet collateral development varies considerably among individuals. Endothelial stress and systemic inflammation are key biological processes involved in collateral vessel formation. The Endothelial Activation and Stress Index (EASIX), calculated from lactate dehydrogenase, creatinine, and platelet count, is a simple marker reflecting endothelial dysfunction and inflammatory status. However, evidence regarding its relationship with angiographic coronary collateral development in CTO remains limited. Therefore, this study aimed to evaluate the association between EASIX and CCC grades in patients with CTO. Methods: This retrospective study included 186 patients with CTO who underwent coronary angiography. CCC was evaluated using the Rentrop–Cohen classification and categorized as poorly developed (grades 0–1) or well-developed (grades 2–3). Clinical and laboratory data, including EASIX, were collected. Univariate and multivariate binary logistic regression analyses were performed to identify factors associated with poorly developed CCC. EASIX was standardized (z-score), and odds ratios were reported per 1-standard deviation increase. The predictive performance of EASIX was assessed using receiver operating characteristic (ROC) curve analysis. Results: Poorly developed CCC was observed in 70 patients (37.6%). Patients with well-developed CCC had significantly lower EASIX values (median 0.44 vs. 0.67, p < 0.001) and higher HDL cholesterol levels (p = 0.043). Neutrophil-to-lymphocyte ratio was also higher in the poorly developed CCC group (median 2.59 [2.19–3.59] vs. 2.41 [1.59–3.49], p = 0.028). In multivariate analysis, standardized EASIX remained independently associated with poorly developed CCC (OR 2.536 per 1-SD increase, 95% CI 1.734–3.710, p < 0.001). ROC analysis showed that EASIX provided moderate discrimination for poorly developed CCC (AUC 0.718), with 72.9% sensitivity and 62.1% specificity at a cutoff of >0.51. Conclusions: Higher EASIX values were independently associated with poorly developed CCC in patients with CTO. These findings support a link between systemic endothelial stress and impaired collateral vessel formation. EASIX may serve as a simple, practical, and low-cost biomarker to support risk stratification in CTO patients; however, prospective studies are needed to confirm these results and clarify clinical implications. Full article

Etrasimod is an oral selective sphingosine-1 phosphate receptor modulator, and its anti-inflammatory mechanism of action in inflammatory bowel diseases is not completely understood. It targets pro-inflammatory immune cells expressing sphingosine-1-phosphate receptors during their migration from the lymphatic system to the circulation and intestinal mucosa. Reductions in certain lymphocyte subsets in the peripheral blood have been reported, but its effects in lymph nodes remain unknown. This study investigated changes in leukocyte subpopulations in peripheral lymph nodes and blood in Crohn’s disease patients treated with etrasimod. Moderate-to-severe Crohn’s disease patients participated in this randomized, double-blind study, within the phase 2 CULTIVATE clinical trial. At baseline and after 14 weeks of etrasimod treatment, peripheral blood and inguinal lymph node biopsies were obtained. Isolated peripheral blood mononuclear cells and lymph node leukocyte populations were analyzed at single cell level using mass cytometry at both timepoints. The immunophenotyping revealed 15 innate and adaptive major immune cell populations, as well as 14 subpopulations of CD4+ and CD8+ T-cells. In peripheral lymph nodes, etrasimod resulted in significant accumulation of naïve, central memory, and effector memory CD4+ T-cells (+10.7%, +4.2%, and +2.3%, respectively; all p = 0.03), as well as naïve CD8+ T-cells (+4.2%; p = 0.03). Conversely, these subsets were reduced in peripheral blood (−6.2%, −6.0%, −2.0%, and −2.2%, respectively; all p = 0.03). Naïve and memory B-cells decreased in the circulation (−1.7%, p = 0.057; −0.6%, p = 0.03, respectively) but were unchanged in the lymph nodes. Innate immune cell populations remained mostly unaffected in both compartments. Our data indicate that etrasimod’s pharmacodynamic effect is related primarily with the attenuation of the T-cell mediated inflammation with minor changes in B-cells. However, additional follow-up studies are needed for the validation of these observations in the context of Crohn’s disease. Full article

Background: Donor lymphocyte infusion (DLI) is commonly used to prevent or treat leukemic relapse following allogeneic hematopoietic cell transplantation; however, efficacy is limited by immune exhaustion, checkpoint-mediated inhibition, and the risk of graft-versus-host disease (GvHD). Gamma delta (γδ) T-cells represent a promising “off-the-shelf” adoptive cell therapy (ACT) with favorable safety and MHC-independent cytotoxicity, yet their function is similarly constrained by the leukemic tumor microenvironment (TME). Acute exercise mobilizes cytotoxic lymphocyte subsets, and is an emerging strategy to enhance cellular immunotherapies, including DLI and expanded γδ T-cells. This study examined how exercise-mobilized lymphocytes and exercise-expanded γδ T-cells interact with TIGIT blockade to improve anti-leukemic activity. Methods: Healthy participants completed an acute cycling bout, after which peripheral blood mononuclear cells (PBMCs) and ex vivo expanded γδ T-cells were phenotyped and cytotoxicity was determined against leukemia cells with TIGIT checkpoint inhibition. The therapeutic relevance of combining TIGIT blockade with rest- or exercise-expanded γδ T-cells was further evaluated in NSG-IL15 mice challenged with K562-luc leukemia. Results: Acute exercise increased circulating CD8⁺ and γδ T-cells with higher TIGIT and PD-1 expression. Exercise-expanded γδ T-cells maintained increased PD-1 and TIGIT expression and exhibited increased co-expression of DNAM-1 and TIGIT. Exercise mobilized PBMCs and exercise-expanded γδ T-cells demonstrated enhanced cytotoxicity, further amplified by TIGIT blockade. In vivo, TIGIT-treated exercise-expanded γδ T-cells modestly improved tumor suppression and prolonged tumor-free survival compared to untreated controls. Conclusions: Exercise primes DLI and γδ T-cell products for enhanced responsiveness to TIGIT checkpoint inhibition. Targeting TIGIT likely augments DNAM-1 dependent cytotoxicity and improves anti-leukemic activity, supporting the integration of exercise-enhanced DLI and γδ T-cell therapies with immune checkpoint blockade as a safe strategy to improve relapse control in leukemia. Full article

Abnormal liver function tests are frequently reported in patients with COVID-19. This study aimed to identify potential treatment-associated hepatocellular injury in COVID-19 patients by dynamically assessing circulating miR-122, a biomarker with high hepatic specificity and sensitivity. An exploratory approach was additionally used, given the limited evidence regarding factors influencing miR-122 expression in this setting. We performed a prospective cohort study including 96 adult participants enrolled at a tertiary hospital in Bucharest, Romania, between March 2022 and July 2023: 78 COVID-19 patients (57 with baseline and follow-up miR-122 assessment after 5 days of treatment and 21 with a single measurement) and 18 non-COVID-19 participants included for comparison. Plasma miR-122 levels were measured using quantitative polymerase chain reaction, normalized to U6 small nuclear RNA, and expressed as log₁₀(2^−ΔCt). No associations were observed between miR-122 expression and remdesivir administered for standard treatment durations (3–5 days) or other COVID-19–specific therapies. However, a duration-dependent relationship with remdesivir cannot be excluded. Moreover, therapeutic paracetamol use prior to presentation was positively associated with miR-122 expression at follow-up and remained significant after adjustment. Additionally, bivariate analyses revealed inverse correlations between baseline miR-122 and inflammatory biomarkers, with multivariable analysis showing an independent positive association with lymphocyte count. Full article

Background/Objectives: The ketogenic diet (KD) has been shown to exert beneficial effects on human immunity by enhancing cytotoxic T lymphocyte function through metabolic reprogramming. However, strict dietary restrictions limit adherence and complicate its use in clinical practice. Exogenous ketone supplements have therefore been promoted as a more feasible alternative to elevate ketone body levels without the need for dietary changes. The objective of this study was to assess whether ketone salt or ketone ester supplementation can reproduce KD-mediated immunometabolic effects on CD8⁺ T cells in healthy individuals. Methods: In a prospective interventional study, healthy volunteers received either ketone salts (KS) or ketone esters (KE) for three weeks. Plasma β-hydroxybutyrate (BHB) concentrations were determined, and CD8⁺ T-cell cytokine secretion, functional responses, and mitochondrial energy metabolism were analyzed. In a subgroup, KS supplementation was combined with a carbohydrate-restricted, non-ketogenic diet. Results: While KS supplementation resulted in a short-lived increase in plasma BHB concentrations followed by increased BHB uptake in immune cells, KE supplementation led to more sustained plasma BHB levels, however, without detectable intracellular BHB accumulation. Neither intervention affected CD8⁺ T-cell cytokine production, functional capacity, or mitochondrial energy metabolism, and KS intake combined with a carbohydrate-restricted, non-ketogenic diet likewise did not alter CD8⁺ T-cell immunometabolic parameters. Conclusions: Transient elevation of circulating ketone body levels through supplementation seems insufficient to reproduce the immunometabolic effects of a KD, which likely require broader metabolic adaptations. Thus, the impact of exogenous ketones on adaptive immunity in healthy individuals appears limited. Full article

The involvement of the immune system in pulmonary fibrosis is established, the precise contributions of tissue-resident memory T (T_RM) cells are still poorly defined. This study sought to define the contribution of CD4⁺ T_RM cells to pulmonary fibrosis, their origin, and regulatory mechanisms. We combined bioinformatic analysis of human fibrotic lung single-cell RNA-sequencing data with experiments in a bleomycin-induced C57BL/6 mouse model. Flow cytometry, targeted in vivo depletion, lymphocyte trafficking blockade, cell co-culture, and pharmacological inhibition were employed. CD4⁺ T_RM cells were observed at higher frequencies within fibrotic lung tissue. Their presence correlated with disease severity, and they were found to exhibit a pro-inflammatory and pro-fibrotic phenotype. Their specific depletion alleviated fibrosis. These cells primarily originated from recruited circulating lymphocytes, as blocking this recruitment reduced T_RM accumulation and attenuated disease. Furthermore, the Notch signaling pathway was activated in fibrotic lung CD4⁺ T_RM cells, and its inhibition suppressed their differentiation and impaired their pro-fibrotic function. We conclude that CD4⁺ T_RM cells are pathogenic drivers in pulmonary fibrosis, originating from circulating precursors and being regulated by Notch signaling, underscoring their relevance for therapeutic intervention. Full article

Epithelial-mesenchymal transition (EMT) is a key driver of invasion, metastasis, and treatment resistance in gastric cancer, yet its post-transcriptional regulation by microRNAs (miRNAs) is not fully delineated. We performed a structured literature search in PubMed, Web of Science, and Scopus for studies evaluating miRNAs in relation to EMT in gastric cancer and synthesised tumor-intrinsic, microenvironmental, and circulating EMT-related miRNA networks. Downregulated, predominantly tumor-suppressive miRNAs, including miR-34a, miR-200 family, miR-148a, miR-204, miR-30a, miR-101, miR-218, miR-26a, miR-375, miR-506, and others, converge on EMT transcription factors and pathways such as ZEB1/2, Snail, TGF-β/SMAD, Wnt/β-catenin, c-Met, and PI3K/AKT, and their restoration reverses EMT phenotypes in preclinical models. Upregulated oncomiRs, such as miR-21, miR-17-5p, miR-106b-5p, miR-23a, miR-130a-3p, miR-196a-5p, miR-181a, miR-616-3p, miR-301a-3p, miR-150, miR-27a-3p and miR-192/215, target tumor suppressors and reinforce these pathways. Cancer-associated fibroblast, macrophage, neutrophil, and natural killer cell-derived miRNAs, together with systemic indices such as the neutrophil-to-lymphocyte ratio and mediators like FAM3C, add microenvironmental layers of EMT regulation. Several EMT-related miRNAs show consistent associations with invasion, metastasis, peritoneal dissemination, prognosis, and chemoresistance, and many are detectable in circulation. Overall, EMT-related miRNAs orchestrate gastric cancer cell plasticity and tumor-microenvironment crosstalk and represent promising biomarker and therapeutic candidates that warrant validation in prospective, subtype-stratified, and translational studies. Full article

Lung cancer is one of the most common malignant tumors and is associated with a high mortality rate, especially in aged patients. Immunotherapy is an effective method for treating lung cancer, particularly when used in combination with other treatments like chemotherapy. One of the types of immunotherapy is the use of autologous immune cells that are pre-activated before injection back to a patient. The effectiveness of this type of immunotherapy is determined by the specificity of its action on cancer cells through the activation of immune cell, e.g., lymphocytes. However, this treatment is not extensively used in elder patients due to higher risk of complications. On the other hand, in those aged patients who suffer from late stage cancer, the immune-cell based immunotherapy may come as a last resort. In this study, we present a clinical case of a 63-year-old patient with advanced-stage lung cancer and CT-confirmed infiltration of the left main bronchus. Treatment of the patient with immunotherapy using autologous activated lymphocytes combined with tomotherapy resulted in prominent improvement and decreased size of the malignancy. This positive effect was accompanied by a decrease in the number of circulating tumor cells in the blood. The patient was treated in May-June 2024 and is still alive with good condition as of August 2025. We conclude that combined treatment is a reliable option for selected aged patients with advanced-stage lung cancer. Full article