Lung cancer remains the leading cause of cancer-related incidence and mortality worldwide. Among its histological subtypes, non-small cell lung cancer (NSCLC) accounts for the majority of cases, representing the predominant pathological type. Notably, in the elderly population, NSCLC continues to be a major contributor to cancer-related deaths. With the global ageing population, immunosenescence has emerged as a key factor influencing the occurrence, progression, and the efficacy of immunotherapy of NSCLC. Immunosenescence refers to the age-related decline in immune system function, which manifests as alterations in both the quantity and functionality of immune cells. These include thymic involution, T cell exhaustion, epigenetic modifications, weakened immune responses, and a chronic low-grade inflammatory state. This review comprehensively analyzes the role of immunosenescence in elderly patients with advanced NSCLC and proposes potential therapeutic strategies to intervene in the immunosenescence process. By targeting immunosenescence, these strategies aim to inhibit the progression of NSCLC and improve the effectiveness of immunotherapy.
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Humans ; Carcinoma, Non-Small-Cell Lung/genetics* ; Immunotherapy ; Lung Neoplasms/genetics* ; Immunosenescence ; Aged

The rise in global life expectancy has led to an increase in the older population, presenting significant challenges in managing infectious diseases. Aging affects the innate and adaptive immune systems, resulting in chronic low-grade inflammation (inflammaging) and immune function decline (immunosenescence). These changes would impair defense mechanisms, increase susceptibility to infections and reduce vaccine efficacy in older adults. Cellular senescence exacerbates these issues by releasing pro-inflammatory factors, further perpetuating chronic inflammation. Moreover, comorbidities, such as cardiovascular disease and diabetes, which are common in older adults, amplify immune dysfunction, while immunosuppressive medications further complicate responses to infections. This review explores the molecular and cellular mechanisms driving inflammaging and immunosenescence, focusing on genomic instability, telomere attrition, and mitochondrial dysfunction. Additionally, we discussed how aging-associated immune alterations influence responses to bacterial, viral, and parasitic infections and evaluated emerging antiaging strategies, aimed at mitigating these effects to improve health outcomes in the aging population.
Humans ; Aging/physiology* ; Communicable Diseases/immunology* ; Immunosenescence/physiology* ; Inflammation/immunology* ; Genomic Instability

Age-associated changes in immune cells have been linked to an increased risk for infection. However, a global and detailed characterization of the changes that human circulating immune cells undergo with age is lacking. Here, we combined scRNA-seq, mass cytometry and scATAC-seq to compare immune cell types in peripheral blood collected from young and old subjects and patients with COVID-19. We found that the immune cell landscape was reprogrammed with age and was characterized by T cell polarization from naive and memory cells to effector, cytotoxic, exhausted and regulatory cells, along with increased late natural killer cells, age-associated B cells, inflammatory monocytes and age-associated dendritic cells. In addition, the expression of genes, which were implicated in coronavirus susceptibility, was upregulated in a cell subtype-specific manner with age. Notably, COVID-19 promoted age-induced immune cell polarization and gene expression related to inflammation and cellular senescence. Therefore, these findings suggest that a dysregulated immune system and increased gene expression associated with SARS-CoV-2 susceptibility may at least partially account for COVID-19 vulnerability in the elderly.
Adult ; Aged ; Aged, 80 and over ; Aging ; genetics ; immunology ; Betacoronavirus ; CD4-Positive T-Lymphocytes ; metabolism ; Cell Lineage ; Chromatin Assembly and Disassembly ; Coronavirus Infections ; immunology ; Cytokine Release Syndrome ; etiology ; immunology ; Cytokines ; biosynthesis ; genetics ; Disease Susceptibility ; Flow Cytometry ; methods ; Gene Expression Profiling ; Gene Expression Regulation, Developmental ; Gene Rearrangement ; Humans ; Immune System ; cytology ; growth & development ; immunology ; Immunocompetence ; genetics ; Inflammation ; genetics ; immunology ; Mass Spectrometry ; methods ; Middle Aged ; Pandemics ; Pneumonia, Viral ; immunology ; Sequence Analysis, RNA ; Single-Cell Analysis ; Transcriptome ; Young Adult

Adult ; Aged ; Aqueous Humor ; virology ; Female ; Humans ; Immunocompetence ; immunology ; Inflammation ; virology ; Male ; Middle Aged ; Retrospective Studies ; Young Adult

Although chronic obstructive pulmonary disease (COPD) is regarded as a chronic inflammatory lung disease, the disease mechanism is still not known. Intriguingly, aging lungs are quite similar to COPD-affected lungs in many ways, and COPD has been viewed as a disease of accelerated premature aging of the lungs. In this paper, based on a literature review, we would like to propose immunosenescence, age-associated decline in immunity, as a critical mechanism for the development of COPD. Immunosenescence can cause a low-grade, systemic inflammation described as inflammaging. This inflammaging may be directly involved in the COPD pathogenesis. The potential contributors to the development of inflammaging in the lungs possibly leading to COPD are discussed in the review paper. A notable fact about COPD is that only 15% to 20% of smokers develop clinically significant COPD. Given that there is a substantial inter-individual variation in inflammaging susceptibility, which is genetically determined and significantly affected by the history of the individual's exposure to pathogens, immunosenescence and inflammaging may also provide the answer for this unexpectedly low susceptibility of smokers to clinically significant COPD.
Aging ; Aging, Premature ; Immunosenescence ; Inflammation ; Lung ; Lung Diseases ; Pulmonary Disease, Chronic Obstructive

Immunosenescence is characterized by a progressive deterioration of the immune system associated with aging. Multiple components of both innate and adaptive immune systems experience aging-related changes, such as alterations in the number of circulating monocytic and dendritic cells, reduced phagocytic activities of neutrophils, limited diversity in B/T cell repertoire, T cell exhaustion or inflation, and chronic production of inflammatory cytokines known as inflammaging. The elderly are less likely to benefit from vaccinations as preventative measures against infectious diseases due to the inability of the immune system to mount a successful defense. Therefore, aging is thought to decrease the efficacy and effectiveness of vaccines, suggesting aging-associated decline in the immunogenicity induced by vaccination. In this review, we discuss aging-associated changes in the innate and adaptive immunity and the impact of immunosenescence on viral infection and immunity. We further explore recent advances in strategies to enhance the immunogenicity of vaccines in the elderly. Better understanding of the molecular mechanisms underlying immunosenescence-related immune dysfunction will provide a crucial insight into the development of effective elderly-targeted vaccines and immunotherapies.
Adaptive Immunity ; Aged ; Aging ; Communicable Diseases ; Cytokines ; Dendritic Cells ; Humans ; Immune System ; Immunosenescence ; Immunotherapy ; Inflation, Economic ; Neutrophils ; Vaccination ; Vaccines

BACKGROUND: The prevalence of acute kidney injury (AKI) in elderly patients has grown considerably. Age-associated changes in the immune system can be one of the critical factors determining AKI outcomes. This study aimed to investigate the role of senescence of bone marrow (BM)-derived cells in the development of AKI, focusing on the immune response. METHODS: Female 7-week-old C57BL/6 mice were irradiated and treated with BM cells from either 48-week-old or 8-week-old male mice. Ischemia-reperfusion injury (IRI) was induced, and their functional deterioration, histological tubular damage, and inflammatory responses were compared. For the in-vitro study, lipopolysaccharide (LPS)-stimulated cytokine production by BM cells from old and young mice were examined. RESULTS: At 24 hours after IRI, there was no significant difference in the number of circulating immune cells between the mice transplanted with old or young BM cells. However, the mice with old BM cells showed less functional deterioration and histological tubular injury than those with young BM cells. Moreover, macrophage infiltration and renal cytokine interleukin (IL)-12 levels were lower in the mice with old BM cells at 24 hours post-IRI. Consistently, the in vitro study showed that LPS-induced production of cytokines interferon-γ, monocyte chemoattractant protein-1, and IL-10 was attenuated in cultured old BM cells, suggesting that age-related functional changes in these cells may lead to reduced inflammation in IRI. CONCLUSION: Immunosenescence could affect the susceptibility and response to renal IRI. Further studies specifically addressing age-related alterations can help in the development of treatment strategies for elderly patients with AKI.
Acute Kidney Injury ; Aged ; Aging ; Animals ; Bone Marrow Cells ; Bone Marrow ; Chemokine CCL2 ; Cytokines ; Female ; Humans ; Immune System ; Immunosenescence ; In Vitro Techniques ; Inflammation ; Interleukin-10 ; Interleukins ; Macrophages ; Male ; Mice ; Prevalence ; Reperfusion Injury

Pyogenic liver abscess (PLA) can be caused by bacteria entering the liver via the portal vein or primary bacteremia, or it can be cryptogenic. Recently, Klebsiella pneumoniae has been increasingly found as a PLA pathogen. PLA due to this bacterium often leads to formation of extrahepatic abscesses. The treatment of choice is dual therapy with insertion of percutaneous catheter drainage and antibiotic therapy. We report 2 cases of PLA due to K. pneumoniae in immunocompetent children. We successfully treated patient 1 with percutaneous catheter drainage for 18 days and 6-week course of antibiotic therapy. Patient 2 was treated with percutaneous needle aspiration and antibiotic therapy for the same period. In both patients, the PLAs showed the ultrasound-confirmed resolutions after the dual therapy.
Abscess ; Anti-Bacterial Agents ; Bacteremia ; Bacteria ; Catheters ; Child ; Drainage ; Humans ; Immunocompetence ; Klebsiella pneumoniae ; Klebsiella ; Liver ; Liver Abscess, Pyogenic ; Needles ; Pneumonia ; Portal Vein

Septic arthritis of acromioclavicular (AC) joint is a rare entity. It is generally seen in patients who are immunocompromised. Only 15 cases have been reported till now, with only one case series of 6 patients. We report a case of septic arthritis of AC joint in an immunocompetent child. A 9 years old girl presented with history of pain in left shoulder for 4 days associated with fever. No history suggestive of any immunocompromised state was complained. On local examination, a swelling of around 3 cm in diameter was found over left AC joint region with raised local temperature, tenderness on palpation and positive response in fluctuation test. Total leukocyte count was 18.7 × 10/L with 80% of neutrophils. Erythrocyte sedimentation rate (ESR) was 28 mm/1 h. C-reactive protein (CRP) was 12 mg/L. X-ray showed enlarged left AC joint space. Ultrasound revealed hypoechoic collection in the AC joint and the surrounding area. The aspirate was thick and purulent in nature, revealing Gram positive cocci at staining. Arthrotomy and thorough lavage of AC joint was done. Culture of the aspirate showed Methicillin Resistant Staphylococcus Aureus (MRSA) after 48 hours that was sensitive to amikacin, gentamicin, erythromycin and teicoplanin. Patient was symptom-free at 2 months of follow-up with no signs of osteomyelitis on the radiographs. Thus this is the first case of AC joint septic arthritis in healthy individual. Being proximal to the shoulder joint, AC joint septic arthritis can be confused with the shoulder joint septic arthritis. Thus, high index of suspicion is required for accurate diagnosis.
Acromioclavicular Joint ; Anti-Bacterial Agents ; therapeutic use ; Arthritis, Infectious ; diagnosis ; therapy ; Child ; Female ; Humans ; Immunocompetence

Intestinal tuberculosis is an infection of the gastrointestinal tract by the Mycobacterium tuberculosis complex. To the best of our knowledge, solitary intestinal tuberculosis accompanied by intestinal obstruction, particularly in the middle of the small intestine, is extremely rare. We report a case of solitary jejunal tuberculosis in a 49-year-old man with no underlying disease. He was admitted a few days after the onset of diffuse abdominal discomfort. Upon evaluation, we initially considered a malignancy of the distal jejunum with ileus due to the presence of a mass. Therefore, he underwent laparoscopic resection of the small bowel. Unexpectedly, the histologic specimen showed a chronic caseating granulomatous lesion with acid-fast bacilli. Ultimately, he was diagnosed with solitary jejunal tuberculosis. He was successfully treated with anti-tuberculosis drugs without any complications.
Gastrointestinal Tract ; Humans ; Ileus ; Immunocompetence ; Intestinal Obstruction* ; Intestine, Small ; Jejunum ; Middle Aged ; Mycobacterium tuberculosis ; Tuberculosis* ; Tuberculosis, Gastrointestinal