Biomarker Research最新文献

Acute myeloid leukemia (AML) remains a formidable blood cancer, despite recent advances in treatment. A significant challenge persists in improving patient outcomes, particularly in addressing relapse and treatment resistance. Identifying new therapeutic targets is critical for advancing AML therapy. C-type lectin-like molecule-1 (CLL-1) has emerged as a promising therapeutic target in AML. This cell surface receptor is highly expressed on AML blasts and demonstrates stable expression throughout disease progression. CLL-1's consistent presence makes it an ideal candidate for monitoring minimal residual disease (MRD), which is a critical indicator for predicting relapse. Beyond its utility as a diagnostic marker, CLL-1 offers exciting potential in the development of immunotherapies. Emerging strategies, such as CAR-T-cell therapy and antibody-drug conjugates (ADCs), are being investigated to leverage the immune system against CLL-1-expressing AML cells. This review examines the structure, function, and expression patterns of CLL-1 in AML and other hematologic malignancies, providing insights into its role in disease pathogenesis and treatment potential. Exploring CLL-1 as a target for diagnosis, MRD monitoring, and immunotherapy opens new avenues for AML treatment. A deeper understanding of its relationship with AML pathogenesis will aid in the development of targeted therapies, offering hope for improved patient outcomes in the future.

Platelets, anucleate blood cells essential for hemostasis, are increasingly recognized for their role in cancer, challenging the traditional notion of their sole involvement in blood coagulation. It has been demonstrated that platelets establish bidirectional communication with tumor cells, contributing to tumor progression and metastasis through diverse molecular mechanisms such as modulation of proliferation, angiogenesis, epithelial-mesenchymal transition, resistance to anoikis, immune evasion, extravasation, chemoresistance, among other processes. Reciprocally, cancer significantly alters platelets in their count and composition, including mRNA, non-coding RNA, proteins, and lipids, product of both internal synthesis and the uptake of tumor-derived molecules. This phenomenon gives rise to tumor-educated platelets (TEPs), which are emerging as promising tools for the development of liquid biopsies. In this review, we provide a detailed overview of the dynamic roles of platelets in tumor development and progression as well as their use in diagnosis and prognosis. We also provide our view on current limitations, challenges and future research areas, including the need to design more efficient strategies for their isolation and analysis, as well as the validation of their sensitivity and specificity through large-scale and rigorous clinical trials. This research will not only enable the evaluation of their clinical viability but could also open new opportunities to enhance diagnostic accuracy and develop personalized treatments in oncology.

Osteoarthritis (OA), a ubiquitous degenerative joint disorder, is marked by pain and disability, profoundly impacting patients' quality of life. As the population ages, the global prevalence of OA is escalating. Omics technologies have become instrumental in investigating complex diseases like OA, offering comprehensive insights into its pathogenesis and progression by uncovering disease-specific alterations across genomics, transcriptomics, proteomics, and metabolomics levels. In this review, we systematically analyzed and summarized the application and recent achievements of omics technologies in OA research by scouring relevant literature in databases such as PubMed. These studies have shed light on new potential therapeutic targets and biomarkers, charting fresh avenues for OA diagnosis and treatment. Furthermore, in our discussion, we highlighted the immense potential of spatial omics technologies in unraveling the molecular mechanisms of OA and in the development of novel therapeutic strategies, proposing future research directions and challenges. Collectively, this study encapsulates the pivotal advances in current OA research and prospects for future investigation, providing invaluable references for a deeper understanding and treatment of OA. This review aims to synthesize the recent progress of omics technologies in the realm of OA, aspiring to furnish theoretical foundations and research orientations for more profound studies of OA in the future.

Background: In both chronic lymphatic leukemia (CLL) and follicular lymphoma (FL) immunotherapy determines B-depletion that leads to temporary suppression of humoral immunity, which is clinically relevant especially during the COVID-19 pandemic, when most patients in the first wave received the BNT162b2 vaccine during anti-neoplastic treatment.

Methods: To capture changes in the immunome and microbiome composition in CLL and FL patients upon mRNA-based vaccination, we designed a prospective, longitudinal study to profile both the humoral and the cellular response after exposure to the BNT162b2 COVID-19 vaccine.

Results: In both CLL patients and FL patients, the second and third administrations of the BNT162b2 vaccine increased the titer of specific antibodies against SARS-CoV-2. In FL patients, vaccination induced expansion of central memory CD8 + CD57dim CD279 + T cells and reduction of the neutrophil subset myeloid 1 (CD14^-CD15⁺CD16^dimCD64⁺CD33^-CD38⁺PDL1⁺HLA-DR^-); in both cohorts, CD45RA + CD27 + CD279 + NK cells were expanded after a full cycle of vaccination. After vaccination, the genera Collinsella, Gemmiger, Lachnospiraceae, Blautia, Ruminococcus and Lactobacillus increased in both CLL patients and FL patients, whereas Faecalibacterium, Enterobacteriacae, and Enterococcus decreased. Multivariate analysis failed to identify factors associated with changes in microbiome communities among the CLL and FL cohorts, considering age, sex, exposure to anti-CD20 therapy and disease activity. Only in FL patients, alpha diversity was negatively correlated with neutrophil subsets myeloid 1 e 5 at baseline and positively correlated with neutrophil subset 6 after vaccination. PICRUSt2 analysis showed how microbiome can also affect the host health promoting chronic inflammation. The L-lysine biosynthesis pathway was more represented in CLL patients, whereas the L-valine degradation pathway and the anaerobic degradation of purine nucleobases were overrepresented in the FL cohort.

Conclusions: Taken together, our findings reveal the effect of the BNT162b2 vaccine in shaping the microbiome composition in CLL and FL patients, despite receiving treatment for their underlying active disease, and highlight the importance of a comprehensive analysis of the immunome and microbiome profiling to understand immune function in these cohorts of patients.

Introduction: Neutrophil gelatinase-associated lipocalin (NGAL) modulates the enzymatic activity of matrix metalloproteinase-9, which is an important mediator of plaque instability in atherosclerosis. High NGAL levels can independently predict all-cause mortality and major adverse cardiac events (MACE) in patients with acute myocardial infarction (AMI). However, studies that have measured NGAL levels in patients with stable coronary artery disease (CAD) are limited. Furthermore, no significant prognostic predictive value between NGAL levels and stable CAD has been established.

Hypothesis: We aimed to investigate the prognostic role of NGAL levels in a prospective cohort study of patients with stable CAD treated with percutaneous coronary intervention (PCI).

Methods: A total of 2,238 stable patients with CAD and a previous PCI were enrolled in a multicenter prospective observational study (The National Taiwan Biosignature Research, NTBR) in Taiwan. The primary outcome was the occurrence of MACE (cardiovascular death, nonfatal myocardial infarction, and ischemic stroke). The secondary outcome was a composite of cardiovascular events (cardiovascular death, nonfatal MI, nonfatal stroke, and hospitalization for heart failure).

Results: During the mean follow-up period of 4.6 ± 1.7 years, 441 patients reached the primary endpoints. Kaplan-Meier analysis showed that event-free survival was significantly different between the first and third tertile groups (log-rank test, p < 0.001) in subjects categorized by NGAL levels. In a multivariate Cox proportional hazard regression analysis, plasma NGAL levels were independently associated with an increased risk of MACE [adjusted hazard ratio (aHR) = 1.35; 95% confidence interval (CI) = 1.18-1.54, p < 0.001], AMI (aHR = 1.34; 95% CI = 1.12-1.59, p < 0.001), and target vessel revascularization (aHR = 1.35; 95% CI = 1.19-1.53, p < 0.001). Addition of serum NGAL levels to the traditional risk model improved its prediction value for future cardiovascular events.

Conclusions: High plasma NGAL levels were independently associated with the occurrence of MACE and composite cardiovascular events in patients with stable PCI-treat CAD.

Adoptive immunotherapy using engineered T cells expressing chimeric antigen receptors has shown remarkable success in treating patients with hematological malignancies. However, realizing broader therapeutic applications of engineered T cells in other diseases requires further exploration in clinical investigations. In this review, we highlight recent advances in the engineering of T cells in non-oncology areas, including autoimmune and inflammatory diseases, infections, fibrosis, hemophilia, and aging. Chimeric antigen receptor immunotherapy has shown good outcomes in non-oncology areas, but many challenges remain in improving its safety and efficacy and and expanding its application to the treatment of non-oncological diseases.

As a member of the Activator Protein-1 (AP-1) transcription factor family, the Basic Leucine Zipper Transcription Factor (BATF) mediates multiple biological functions of immune cells through its involvement in protein interactions and binding to DNA. Recent studies have demonstrated that BATF not only plays pivotal roles in innate and adaptive immune responses but also acts as a crucial factor in the differentiation and function of various immune cells. Lines of evidence indicate that BATF is associated with the onset and progression of allergic diseases, graft-versus-host disease, tumors, and autoimmune diseases. This review summarizes the roles of BATF in the development and function of innate and adaptive immune cells, as well as its immunoregulatory effects in the development of autoimmune diseases, which may enhance the current understanding of the pathogenesis of autoimmune diseases and facilitate the development of new therapeutic strategies.

Background: The combination of conventional chemotherapy and immune checkpoint inhibitors (ICIs) has been unsuccessful for pancreatic ductal adenocarcinoma (PDAC). Administration of maximum tolerated dose of chemotherapy drugs may have immunosuppressive effects.

Methods: We thus tested, by using the preclinical model of PDACs including the genetically engineered mouse KPC spontaneous pancreatic tumor model and the pancreatic KPC tumor orthotopic implant model, the combinations of synthetic innate immune agonists including STING and NLRP3 agonist, respectively, and ICIs with or without chemotherapy.

Results: We found that innate agonists potentiate the role of chemotherapy in inducing effector T cells and subsequently to prime the tumor microenvironment (TME) better for ICI treatments. Triple combination of chemotherapy, innate agonists, and ICIs is superior to single modalities or double modalities in antitumor efficacies. Adding chemotherapy to innate agonists enhances the infiltration of overall CD8⁺ T cells and the memory cytotoxic subtype. NLRP3 agonist has a less effect than STING agonist on driving the T cell exhaustion. Adding chemotherapy to innate agonists enhances the infiltration of dendritic cells (DCs) in the tumors and CD86⁺ mature DCs in tumor draining lymph nodes. RNA sequencing analysis of the pancreatic tumors demonstrates the role of the combination of STING/NLRP3 agonist and chemotherapy, but not either treatment modality alone, in upregulating the T cell activation signaling. The NLRP3 agonist-mediated T cell activation is likely through regulating the nitrogen metabolism pathways.

Conclusion: This study supports the clinical testing of both STING and NLRP3 agonists, respectively, in combination with chemotherapy to sensitize PDAC patients for ICI treatments.

Macrophages are pivotal in the body's defense and response to inflammation. They are present in significant numbers and are widely implicated in various diseases, including cancer. While molecular and histological techniques have advanced our understanding of macrophage biology, their precise function within the cancerous microenvironments remains underexplored. Enhancing our knowledge of macrophages and the dynamics of their extracellular vesicles (EVs) in cancer development can potentially improve therapeutic management. Notably, macrophages have also been harnessed to deliver drugs. Noninvasive in vivo molecular imaging of macrophages is crucial for investigating intricate cellular processes, comprehending the underlying mechanisms of diseases, tracking cells and EVs' migration, and devising macrophage-dependent drug-delivery systems in living organisms. Thus, in vivo imaging of macrophages has become an indispensable tool in biomedical research. The integration of multimodal imaging approaches and the continued development of novel contrast agents hold promise for overcoming current limitations and expanding the applications of macrophage imaging. This study comprehensively reviews several methods for labeling macrophages and various imaging modalities, assessing the merits and drawbacks of each approach. The review concludes by offering insights into the applicability of molecular imaging techniques for real time monitoring of macrophages in preclinical and clinical scenarios.