Biomarker Research最新文献

Platelets are essential for blood clotting and maintaining normal hemostasis. In pathological conditions, platelets are increasingly recognized as crucial regulatory factors in various immune-mediated inflammatory diseases. Resting platelets are induced by various factors such as immune complexes through Fc receptors, platelet-targeting autoantibodies and other platelet-activating stimuli. Platelet activation in immunological processes involves the release of immune activation stimuli, antigen presentation and interaction with immune cells. Platelets participate in both the innate immune system (neutrophils, monocytes/macrophages, dendritic cells (DCs) and Natural Killer (NK) cells and the adaptive immune system (T and B cells). Clinical therapeutic strategies include targeting platelet activation, platelet-immune cell interaction and platelet-endothelial cell interaction, which display positive development prospects. Understanding the mechanisms of platelets in immunity is important, and developing targeted modulations of these mechanisms will pave the way for promising therapeutic strategies.

Triple-negative breast cancer (TNBC) is a subtype of breast cancer known for its high aggressiveness and poor prognosis. Conventional treatment of TNBC is challenging due to its heterogeneity and lack of clear targets. Recent advancements in immunotherapy have shown promise in treating TNBC, with immune checkpoint therapy playing a significant role in comprehensive treatment plans. The tumor microenvironment (TME), comprising immune cells, stromal cells, and various cytokines, plays a crucial role in TNBC progression and response to immunotherapy. The high presence of tumor-infiltrating lymphocytes and immune checkpoint proteins in TNBC indicates the potential of immunotherapeutic strategies. However, the complexity of the TME, while offering therapeutic targets, requires further exploration of its multiple roles in immunotherapy. In this review, we discuss the interaction mechanism between TME and TNBC immunotherapy based on the characteristics and composition of TME, and elaborate on and analyze the effect of TME on immunotherapy, the potential of TME as an immune target, and the ability of TME as a biomarker. Understanding these dynamics will offer new insights for enhancing therapeutic approaches and investigating stratification and prognostic markers for TNBC patients.

Chronic lymphocytic leukemia (CLL) is prevalent in adults and is characterized by the accumulation of mature B cells in the blood, bone marrow, lymph nodes, and spleens. Recent progress in therapy and the introduction of targeted treatments [inhibitors of Bruton's tyrosine kinase (BTKi) or inhibitor of anti-apoptotic B-cell lymphoma-2 (Bcl-2i) protein (venetoclax)] in place of chemoimmunotherapy have significantly improved the outcomes of patients with CLL. These advancements have shifted the importance of traditional predictive markers, leading to a greater focus on resistance genes and reducing the significance of mutations, such as TP53 and del(17p). Despite the significant progress in CLL treatment, some patients still experience disease relapse. This is due to the substantial heterogeneity of CLL as well as the interconnected genetic resistance mechanisms and pathway adaptive resistance mechanisms to targeted therapies in CLL. Although the knowledge of the pathomechanism of CLL has expanded significantly in recent years, the precise origins of CLL and the interplay between various genetic factors remain incompletely understood, necessitating further research. This review enhances the molecular understanding of CLL by describing how BCR signalling, NF-κB PI3K/AKT, and ROR1 pathways sustain CLL cell survival, proliferation, and resistance to apoptosis. It also presents genetic and pathway-adaptive resistance mechanisms in CLL. Identifying B-cell receptor (BCR) signalling as a pivotal driver of CLL progression, the findings advocate personalized treatment strategies based on molecular profiling, emphasizing the need for further research to unravel the complex interplay between BCR signalling and its associated pathways to improve patient outcomes.

The immune system continuously interacts with tumors, possibly leading to systemic alterations in circulating immune cells. However, the potential of these cancer-associated changes for diagnostic purposes remains poorly explored. To investigate this, we conducted a comprehensive flow cytometric analysis of 452 peripheral blood mononuclear cell (PBMC) samples from 206 non-small-cell lung cancer (NSCLC) patients, 100 small-cell lung cancer (SCLC) patients, 94 healthy individuals, and 52 benign lung disease (BLD) patients. We focused specifically on circulating T cells, given their close interaction with tumors, and initially assessed 93 T-cell features from the flow cytometric analysis. Using a feature selection protocol, we identified five T-cell features in peripheral blood with strong diagnostic relevance. Notably, while individual alterations in these features lacked cancer specificity, simultaneous alterations were uniquely indicative of lung cancer. To comprehensively analyze these features, we developed a scoring model, "IMmunoPhenotypic Analysis for Cancer deTection (IMPACT)." Comprehensive analysis using the five features (IMPACT-5) demonstrated high cancer specificity and biomarker efficacy, as evidenced by the high area under the receiver operating characteristic curve values for lung cancer patients (0.9187, 0.9277, and 0.9363 for stage I NSCLC, stage IV NSCLC, and SCLC patients, respectively), in stark contrast to BLD patients (0.5212). These findings suggest that comprehensive analysis of cancer-associated changes in circulating T cells can effectively detect lung cancer from its early stages, proposing immunophenotypic analysis of circulating T cells as an innovative liquid biopsy-based diagnostic biomarker.

Burn injuries represent a significant global challenge due to their multifaceted nature, characterized by a complex cascade of metabolic and immune dysfunction that can result in severe complications. If not identified and managed promptly, these complications can escalate, often leading to fatal outcomes. This underscores the critical importance of timely and precise diagnosis. Fortunately, biomarkers for burn-induced pathologies and outcomes have emerged as powerful diagnostic and prognostic tools. These biomarkers enable early diagnosis and intervention, facilitate risk assessment, support patient-specific treatment, monitoring of disease progression, and therapeutic efficacy, ultimately contributing to improved patient outcomes. However, while previous studies have provided valuable biomarkers for the detection of burn-induced pathologies, many of these were constrained by the techniques and sample sizes available at the time, which can limit the generalizability of the findings. This review highlights numerous biomarkers studied in the literature to date, underscoring the need to replicate these findings in more diverse and representative populations. It also emphasizes the importance of advancing research efforts to develop more efficient, accurate, and cost-effective approaches for integrating biomarkers into clinical practice.

The leukocyte immunoglobulin-like receptor B (LILRB) proteins, characterized by their transmembrane nature and canonical immunoreceptor tyrosine-based inhibitory motifs (ITIM) signaling, play a pivotal role in maintaining immune homeostasis and are implicated in the pathogenesis of various disease states. This comprehensive review will focus on the intricate involvement of the LILRB family in hematologic malignancies. These receptors have emerged as valuable diagnostic and prognostic biomarkers in leukemia, lymphoma, and myeloma. Beyond their prognostic implications, LILRBs actively shape the immune microenvironment and directly influence the disease pathogenesis of hematologic malignancies. Furthermore, their identification as potential therapeutic targets offer a promising avenue for precision medicine strategies in the treatment of these disorders. Currently, multiple LILRB directed therapies are in the preclinical and clinical trial pipelines. This review underscores the multifaceted role of the LILRB family in hematologic malignancies, highlighting their significance from diagnostic and prognostic perspectives to their broader impact on disease pathophysiology and as valuable therapeutic targets.

Harnessing the power of the immune system to target cancer cells is one of the most appealing approaches for cancer therapy. Among these immunotherapies, messenger ribonucleic acid (mRNA) cancer vaccines are worthy of consideration, as they have demonstrated promising results in clinical trials. These vaccines have proven to be safe and well-tolerated. They can be easily mass-produced in a relatively short time and induce a systemic immune response effective against both the primary tumor and metastases. Transcripts encoding immunomodulatory molecules can also be incorporated into the mRNA, enhancing its efficacy. On the other hand, there are some challenges associated with their application, including mRNA instability, insufficient uptake by immune cells, and intrinsic immunogenicity, which can block mRNA translation. Many innovations have been suggested to overcome these obstacles, including structural modification (such as 5' cap modification), optimizing delivery vehicles (especially dendritic cells (DCs) and nanoparticles), and using antigens that can enhance immunogenicity by circumventing tolerance mechanisms. A popular approach is to combine mRNA cancer vaccines with traditional and novel cancer treatments like chemotherapy, radiotherapy, and immune checkpoint blockade (ICB). They are most efficacious when combined with other therapies like ICBs. There is still a long way to go before these vaccines enter the standard of care for cancer patients, but with the incredible pace of development in this field, their clinical application will soon be witnessed. This review highlights the recent advances and challenges of mRNA cancer vaccines. Finally, some of the most prominent clinical applications of these vaccines will be reviewed.

Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) technology is a groundbreaking and dynamic molecular tool for DNA and RNA "surgery". CRISPR/Cas9 is the most widely applied system in oncology research. It is a major advancement in genome manipulation due to its precision, efficiency, scalability and versatility compared to previous gene editing methods. It has shown great potential not only in the targeting of oncogenes or genes coding for immune checkpoint molecules, and in engineering T cells, but also in targeting epigenomic disturbances, which contribute to cancer development and progression. It has proven useful for detecting genetic mutations, enabling the large-scale screening of genes involved in tumor onset, progression and drug resistance, and in speeding up the development of highly targeted therapies tailored to the genetic and immunological profiles of the patient's tumor. Furthermore, the recently discovered Cas12 and Cas13 systems have expanded Cas9-based editing applications, providing new opportunities in the diagnosis and treatment of cancer. In addition to traditional cis-cleavage, they exhibit trans-cleavage activity, which enables their use as sensitive and specific diagnostic tools. Diagnostic platforms like DETECTR, which employs the Cas12 enzyme, that cuts single-stranded DNA reporters, and SHERLOCK, which uses Cas12, or Cas13, that specifically target and cleave single-stranded RNA, can be exploited to speed up and advance oncological diagnostics. Overall, CRISPR platform has the great potential to improve molecular diagnostics and the functionality and safety of engineered cellular medicines. Here, we will emphasize the potentially transformative impact of CRISPR technology in the field of oncology compared to traditional treatments, diagnostic and prognostic approaches, and highlight the opportunities and challenges raised by using the newly introduced CRISPR-based systems for cancer diagnosis and therapy.

The TAM receptor tyrosine kinase family member AXL plays critical roles in tissue homeostasis, survival, chemoresistance, and motility. This study investigates the receptor expression in six AML cell lines and bone marrow myeloblasts from 25 patients with myeloid neoplasms. We found that AXL expression was generally absent or very low in AML myeloblasts. These findings suggest that the efficacy of AXL inhibitors may not depend on AXL positivity but rather on alternative therapeutic mechanisms, such as inducing significant immune responses.