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Gastric Cancer : Official Journal of... Nov 2023The status of regional tumour draining lymph nodes (LN) is crucial for prognostic evaluation in gastric cancer (GaC) patients. Changes in lymph node microarchitecture,... (Meta-Analysis)
Meta-Analysis Review
The clinical importance of the host anti-tumour reaction patterns in regional tumour draining lymph nodes in patients with locally advanced resectable gastric cancer: a systematic review and meta-analysis.
BACKGROUND
The status of regional tumour draining lymph nodes (LN) is crucial for prognostic evaluation in gastric cancer (GaC) patients. Changes in lymph node microarchitecture, such as follicular hyperplasia (FH), sinus histiocytosis (SH), or paracortical hyperplasia (PH), may be triggered by the anti-tumour immune response. However, the prognostic value of these changes in GaC patients is unclear.
METHODS
A systematic search in multiple databases was conducted to identify studies on the prognostic value of microarchitecture changes in regional tumour-negative and tumour-positive LNs measured on histopathological slides. Since the number of GaC publications was very limited, the search was subsequently expanded to include junctional and oesophageal cancer (OeC).
RESULTS
A total of 28 articles (17 gastric cancer, 11 oesophageal cancer) met the inclusion criteria, analyzing 26,503 lymph nodes from 3711 GaC and 1912 OeC patients. The studies described eight different types of lymph node microarchitecture changes, categorized into three patterns: hyperplasia (SH, FH, PH), cell-specific infiltration (dendritic cells, T cells, neutrophils, macrophages), and differential gene expression. Meta-analysis of five GaC studies showed a positive association between SH in tumour-negative lymph nodes and better 5-year overall survival. Pooled risk ratios for all LNs showed increased 5-year overall survival for the presence of SH and PH.
CONCLUSIONS
This systematic review suggests that sinus histiocytosis and paracortical hyperplasia in regional tumour-negative lymph nodes may provide additional prognostic information for gastric and oesophageal cancer patients. Further studies are needed to better understand the lymph node reaction patterns and explore their impact of chemotherapy treatment and immunotherapy efficacy.
Topics: Humans; Stomach Neoplasms; Hyperplasia; Histiocytosis, Sinus; Clinical Relevance; Lymph Nodes; Prognosis; Esophageal Neoplasms; Neoplasm Staging
PubMed: 37776394
DOI: 10.1007/s10120-023-01426-w -
Cureus Aug 2023Tumor necrosis factor-alpha (TNF-α) inhibitors have been shown to be well tolerated among patients with rheumatoid arthritis, inflammatory bowel disease, and psoriasis.... (Review)
Review
Tumor necrosis factor-alpha (TNF-α) inhibitors have been shown to be well tolerated among patients with rheumatoid arthritis, inflammatory bowel disease, and psoriasis. Meanwhile, more recently, clinical practice and research efforts have uncovered increasing cases of psoriatic lesion development tied to initiating treatment with a TNF-α inhibitor. The underlying mechanisms associated with this occurrence have yet to be fully elucidated. A review and analysis of cases of paradoxical psoriasis currently published in the literature is warranted. In addition, exploring possible mechanisms of action and potential treatment options associated with favorable outcomes is much needed. A systematic literature review was performed utilizing PubMed and Google Scholar databases (1992-present), in which 106 cases of paradoxical psoriasis were reviewed. The most common morphology developed was plaque psoriasis vulgaris. There was a female predominance (61.3%), and the most common underlying autoimmune disease was rheumatoid arthritis (45.3%). In addition, the most commonly associated drug with the onset of psoriatic lesions was infliximab (62.3%). Furthermore, the findings suggest that the most well-supported mechanism of action involves the uncontrolled release of interferon-alpha (IFN-α) from plasmacytoid dendritic cells (pDCs) after TNF-α inhibition. While TNF-α inhibitors have been shown to have great benefits to patients with rheumatologic diseases, cases of paradoxical psoriasis demonstrate the importance of close monitoring of patients on TNF-α inhibitors to allow for early recognition, treatment, and potentially change to a different mechanism of action of the medication used to prevent further progression of the inflammatory lesions.
PubMed: 37664349
DOI: 10.7759/cureus.42791 -
Oral Oncology May 2024Recurrent/Metastatic Nasopharyngeal Carcinoma (RM-NPC) remains difficult to treat and contributes to considerable mortality. The first-line treatment for RM-NPC is... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Recurrent/Metastatic Nasopharyngeal Carcinoma (RM-NPC) remains difficult to treat and contributes to considerable mortality. The first-line treatment for RM-NPC is Gemcitabine and Cisplatin and second-line treatment options differ. The endemic variant of NPC is associated with Epstein-Barr Virus (EBV). Therefore, Cell-based Immunotherapy (CBI) targeting EBV-specific RM-NPC may be effective.
METHODS
We systematically searched PubMed, Embase and the Cochrane Library for randomised or observational studies investigating the efficacy and safety of CBI in the treatment of RM-NPC. We performed all meta-analyses using the random-effects model. Studies were further stratified by endemicity, nature of disease and drug type to investigate for potential between-study heterogeneity and additional pre-specified tests were employed to assess for publication bias.
RESULTS
We screened 1,671 studies and included 13 studies with 403 participants in the systematic review, of which nine studies were eligible for meta-analysis. The use of CBI monotherapy as second or subsequent line treatment for EBV-positive RM-NPC revealed an ORR of 10 % (95 %CI = 3 %-29 %), median PFS of 2.37 months (95 %CI = 1.23-3.51) and median OS of 10.16 months (95 %CI = 0.67-19.65). For EBV-specific Cytotoxic T-Lymphocyte monotherapy, the pooled PD rate was 54 % (95 %CI = 9 %-93 %), SD rate was 22 % (95 %CI = 2 %-75 %) and incidence rate of any grade adverse events was 45 %. For Dendritic Cell monotherapy, a PD rate of 80 % (95 % CI = 29 %-98 %), SD rate of 11 % (95 % CI = 0 %-82 %) and incidence rate of any grade adverse events of 29 % was achieved.
CONCLUSION
CBI monotherapy demonstrates some activity in pre-treated RM-NPC. More trials are needed to better understand how to integrate CBI into RM-NPC care.
Topics: Humans; Cell- and Tissue-Based Therapy; Herpesvirus 4, Human; Immunotherapy; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Neoplasm Metastasis; Neoplasm Recurrence, Local; Treatment Outcome
PubMed: 38615584
DOI: 10.1016/j.oraloncology.2024.106786 -
Survey of Ophthalmology 2024Although there have been numerous innovations in the management of retinal detachment (RD) over the past decades, there is still limited understanding of the... (Review)
Review
Although there have been numerous innovations in the management of retinal detachment (RD) over the past decades, there is still limited understanding of the pathophysiological processes that take place before and after repair. Summarizing key concepts using animal studies may allow for a better assessment of common pre- and postoperative microstructural abnormalities in RD. We performed a systematic literature review on Ovid MEDLINE, EMBASE, and Cochrane Controlled Register of Trials from January 1968 to January 2022, searching animal or human studies reporting retinal histologic changes following primary or induced RD. Thirty-two studies were included. Main cellular events were summarized: photoceptor apoptosis occurs as early as 12 hours after RD and, although most cells survive, there is extensive remodeling. Outer segments progressively degenerate, while inner segments are reorganized. Rod and cone opsins are redistributed, and rod axons retract while cones undergo changes in shape. Second- and third-order neurons rearrange their dendritic processes, and Müller cells become hypertrophic, growing into the subretinal space. Finally, retinal pigment epithelium cells undergo a change in their morphology. Acknowledging critical morphologic changes following RD is crucial in understanding why anatomical and functional outcomes can vary. Insights from histological studies, together with high-resolution imaging, may be key in identifying novel biomarkers in RD.
Topics: Animals; Humans; Retinal Detachment; Retina; Retinal Cone Photoreceptor Cells; Retinal Degeneration
PubMed: 37652188
DOI: 10.1016/j.survophthal.2023.08.001 -
Oncology Reviews 2024Malignant gliomas are known with poor prognosis and low rate of survival among brain tumors. Resection surgery is followed by chemotherapy and radiotherapy in treatment...
BACKGROUND
Malignant gliomas are known with poor prognosis and low rate of survival among brain tumors. Resection surgery is followed by chemotherapy and radiotherapy in treatment of gliomas which is known as the conventional treatment. However, this treatment method results in low survival rate. Vaccination has been suggested as a type of immunotherapy to increase survival rate of glioma patients. Different types of vaccines have been developed that are mainly classified in two groups including peptide vaccines and cell-based vaccines. However, there are still conflicts about which type of vaccines is more efficient for malignant glioma treatment.
METHODS
Phase Ⅰ/Ⅱ clinical trials which compared the efficacy and safety of various vaccines with conventional treatments were searched in databases through November 2022. Overall survival (OS) rate, progression free survival (PFS), and OS duration were used for calculation of pooled risk ratio (RR). In addition, fatigue, headache, nausea, diarrhea, and flu-like syndrome were used for evaluating the safety of vaccines therapy in glioma patients.
RESULTS
A total of twelve articles were included in the present meta-analysis. Comparison of OS rate between vaccinated groups and control groups who underwent only conventional treatments showed a significant increase in OS rate in vaccinated patients (I = 0%, RR = 11.17, 95% CI: 2.460-50.225). PFS rate was better in vaccinated glioma patients (I = 83%, RR = 2.87, 95% CI: 1.63-5.03). Assessment of safety demonstrated that skin reaction (I = 0.0%, RR = 3.654; 95% CI: 1.711-7.801, -value = 0.0058) and flu-like syndrome were significantly more frequent adverse effects win vaccinated groups compared to the control group. Subgroup analysis also showed that vaccination leads to better OS duration in recurrent gliomas than primary gliomas, and in LGG than HGG (-value = 0). On the other hand, personalized vaccines showed better OS duration than non-personalized vaccines (-value = 0).
CONCLUSION
Vaccination is a type of immunotherapy which shows promising efficacy in treatment of malignant glioma patients in terms of OS, PFS and duration of survival. In addition, AFTV, peptide, and dendritic cell-based vaccines are among the most efficient vaccines for gliomas. Personalized vaccines also showed considerable efficacy for glioma treatments.
PubMed: 38707486
DOI: 10.3389/or.2024.1374513 -
Clinical Immunology (Orlando, Fla.) May 2024Rheumatoid arthritis (RA) is a systemic chronic autoimmune disease that primarily affects the joints and surrounding soft tissues, characterized by chronic inflammation... (Review)
Review
Rheumatoid arthritis (RA) is a systemic chronic autoimmune disease that primarily affects the joints and surrounding soft tissues, characterized by chronic inflammation and proliferation of the synovium. Various immune cells are involved in the pathophysiology of RA. The complex interplay of factors such as chronic inflammation, genetic susceptibility, dysregulation of serum antibody levels, among others, contribute to the complexity of the disease mechanism, disease activity, and treatment of RA. Recently, the cytokine storm leading to increased disease activity in RA has gained significant attention. Interleukin-33 (IL-33), a member of the IL-1 family, plays a crucial role in inflammation and immune regulation. ST2 (suppression of tumorigenicity 2 receptor), the receptor for IL-33, is widely expressed on the surface of various immune cells. When IL-33 binds to its receptor ST2, it activates downstream signaling pathways to exert immunoregulatory effects. In RA, IL-33 regulates the progression of the disease by modulating immune cells such as circulating monocytes, tissue-resident macrophages, synovial fibroblasts, mast cells, dendritic cells, neutrophils, T cells, B cells, endothelial cells, and others. We have summarized and analyzed these findings to elucidate the pathways through which IL-33 regulates RA. Furthermore, IL-33 has been detected in the synovium, serum, and synovial fluid of RA patients. Due to inconsistent research results, we conducted a meta-analysis on the association between serum IL-33, synovial fluid IL-33, and the risk of developing RA in patients. The pooled SMD was 1.29 (95% CI: 1.15-1.44), indicating that IL-33 promotes the onset and pathophysiological progression of RA. Therefore, IL-33 may serve as a biomarker for predicting the risk of developing RA and treatment outcomes. As existing drugs for RA still cannot address drug resistance in some patients, new therapeutic approaches are needed to alleviate the significant burden on RA patients and healthcare systems. In light of this, we analyzed the potential of targeting the IL-33/ST2-related signaling pathway to modulate immune cells associated with RA and alleviate inflammation. We also reviewed IL-33 and RA susceptibility-related single nucleotide polymorphisms, suggesting potential involvement of IL-33 and macrophage-related drug-resistant genes in RA resistance therapy. Our review elucidates the role of IL-33 in the pathophysiology of RA, offering new insights for the treatment of RA.
PubMed: 38825072
DOI: 10.1016/j.clim.2024.110264 -
Frontiers in Pharmacology 2024Despite extensive literature on therapeutic strategies for cervical cancer, a bibliometric analysis specifically focused on immunotherapy for advanced, recurrent, or...
A comprehensive bibliometric analysis (2000-2022) on the mapping of knowledge regarding immunotherapeutic treatments for advanced, recurrent, or metastatic cervical cancer.
BACKGROUND
Despite extensive literature on therapeutic strategies for cervical cancer, a bibliometric analysis specifically focused on immunotherapy for advanced, recurrent, or metastatic (A/R/M) cervical malignancies remains unexplored. This study aims to address this gap by presenting a comprehensive overview that includes general characteristics, research focal points, the trajectory of evolution, and current emerging trends in this under-researched area.
METHODS
A systematic search was conducted using the Web of Science Core Collection (WOSCC) to identify articles related to A/R/M cervical cancer published between 2000 and 2022. Citespace and VOS viewer were the primary tools used to identify research focal points, intriguing future patterns, and to evaluate contributions and co-occurrences among authors, institutions, countries, and journals.
RESULTS
A total of 1,001 original articles were identified, involving 6,387 authors from 66 countries and 1,474 institutions, and published across 366 academic journals. The United States contributed most significantly. The most productive researcher was Van der Burg SH from Leiden University Medical Center. The International Journal of Cancer and Cancer Research were identified as the most productive and influential journals, respectively. Analysis of co-citation clusters highlighted 25 clusters, primarily focusing on potential predictive biomarkers, dendritic cell-based tumor vaccines, therapeutic HPV vaccinations, peptide-based cancer vaccines, tumor immune microenvironments, and adoptive cell transfer (ACT). The latest significant trends in A/R/M cervical cancer immunotherapy research included ACT, CAR-T, and immune checkpoint inhibitors (ICIs), as revealed by keyword and reference burst detection.
CONCLUSION
This pioneering study provides a detailed landscape of immunotherapy research in A/R/M cervical cancer. It underscores the importance of global collaboration, enriches our understanding of the immunology of A/R/M cervical cancer, expands on potential beneficiaries of immunotherapy, and explores clinical applications of various therapies, including therapeutic vaccines, adoptive cell transfer, and ICIs, particularly in combination with established treatments such as chemotherapy, radiotherapy, and targeted therapy.
PubMed: 38799160
DOI: 10.3389/fphar.2024.1351363 -
International Immunopharmacology Mar 2024Immune checkpoint inhibitors (ICIs) have effectively improved the clinical outcome of advanced non-small cell lung cancer (NSCLC). Opioids are commonly used for pain... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Immune checkpoint inhibitors (ICIs) have effectively improved the clinical outcome of advanced non-small cell lung cancer (NSCLC). Opioids are commonly used for pain relief in cancer patients. This study aims to clarify the prognostic impact of opioid use in advanced NSCLC patients receiving ICI therapy.
METHODS
A systematic literature review was carried out using online databases before July 2023. The meta-analysis was used to clarify the correlation of opioid use with the overall survival (OS) or progression-free survival (PFS) of ICI-treated NSCLC patients, both of which were determined using hazard ratios (HRs) coupled with 95 % confidence intervals (CIs). Then, an independent cohort enrolling 181 NSCLC patients was utilized for validation. Finally, a comprehensive bioinformatics analysis based on TCGA cohort was performed to investigate the prognostic significance of opioid target genes (OTGs) and their correlation with immune infiltration in NSCLC patients.
RESULTS
A total of 8 studies enrolling 1174 patients were included in the meta-analysis. Opioid use was negatively associated with worse PFS (HR = 2.16, 95 %CI: 1.26-3.71) and OS (HR = 2.02, 95 %CI: 1.54-2.63) in ICI-treated NSCLC patients. The retrospective validation confirmed the above result and identified opioid use as an independent unfavorable predictor for PFS and OS in both the entire cohort and ICI subgroup. The bioinformatic analysis identified 14 prognostic OTGs (CYP17A1, PDYN, PYCARD, FGA, NTSR1, FABP1, HPCA, PENK, PDGFB, LIN7A, FKBP5, TYMS, CACNA1H and LDHA), most of which were correlated with immune infiltration in NSCLC. A risk model was constructed based on 14 OTGs and found to effectively stratify the clinical outcome in both the training and validation set, independent of age, gender and TNM staging system. The model was also significantly correlated with infiltration of activated dendritic cells, neutrophils and tumor infiltrating lymphocytes. Finally, a nomogram was constructed based on the model, age, gender and TNM stage, which could predict well the 1-, 3- and 5-year survival of NSCLC patients.
CONCLUSION
Opioid use is correlated with the poor clinical outcome in ICI-treated NSCLC patients. Precise pain management is highly advocated and opioids are recommended to be cautiously used in these patients. OTGs have the potential to be prognostic biomarkers for NSCLC patients and their role in tumor immunity needs to be further investigated.
Topics: Humans; Analgesics, Opioid; Carcinoma, Non-Small-Cell Lung; Immune Checkpoint Inhibitors; Lung Neoplasms; Membrane Proteins; Opioid-Related Disorders; Retrospective Studies; Vesicular Transport Proteins
PubMed: 38325047
DOI: 10.1016/j.intimp.2024.111611 -
Current Pharmaceutical Design 2024Co-signaling and adhesion molecules are important elements for creating immune synapses between T lymphocytes and antigen-presenting cells; they positively or negatively...
BACKGROUND
Co-signaling and adhesion molecules are important elements for creating immune synapses between T lymphocytes and antigen-presenting cells; they positively or negatively regulate the interaction between a T cell receptor with its cognate antigen, presented by the major histocompatibility complex.
OBJECTIVES
We conducted a systematic review on the effects of High Efficacy Disease Modifying Drugs (HEDMDs) for Multiple Sclerosis (MS) on the co-signaling and adhesion molecules that form the immune synapse.
METHODS
We searched EMBASE, MEDLINE, and other sources to identify clinical or preclinical reports on the effects of HEDMDs on co-signaling and adhesion molecules that participate in the formation of immune synapses in patients with MS or other autoimmune disorders. We included reports on cladribine tablets, anti- CD20 monoclonal antibodies, S1P modulators, inhibitors of Bruton's Tyrosine Kinase, and natalizumab.
RESULTS
In 56 eligible reports among 7340 total publications, limited relevant evidence was uncovered. Not all co-signaling and adhesion molecules have been studied in relation to every HEDMD, with more data being available on the anti-CD20 monoclonal antibodies (that affect CD80, CD86, GITR and TIGIT), cladribine tablets (affecting CD28, CD40, ICAM-1, LFA-1) and the S1P modulators (affecting CD86, ICAM-1 and LFA-1) and less on Natalizumab (affecting CD80, CD86, CD40, LFA-1, VLA-4) and Alemtuzumab (affecting GITR and CTLA-4).
CONCLUSION
The puzzle of HEDMD effects on the immune synapse is far from complete. The available evidence suggests that distinguishing differences exist between drugs and are worth pursuing further.
Topics: Animals; Humans; Cell Adhesion Molecules; Immunological Synapses; Multiple Sclerosis
PubMed: 38343058
DOI: 10.2174/0113816128288102240131053205 -
Frontiers in Pharmacology 2024Photodynamic therapy (PDT) is a minimally invasive treatment approach for precancerous and cancerous lesions, known for its ability to activate the host immune...
Photodynamic therapy (PDT) is a minimally invasive treatment approach for precancerous and cancerous lesions, known for its ability to activate the host immune response. This study conducted a bibliometric analysis to identify the research trends and hotspots related to the immune response in PDT. We analyzed articles and reviews published from 1989 to 2023, retrieved from the Web of Science database. Using Citespace and VOSviewer, we visualized the distribution patterns of these studies in time and space. The analysis revealed a substantial increase in the number of publications on PDT-related immune response since 1989. A total of 1,688 articles from 1,701 institutions were included in this analysis. Among thei nstitutions, the Chinese Academy of Sciences demonstrated exceptional productivity and a willingness to collaborate with others. Additionally, 8,567 authors contributed to the field, with Mladen Korbelik, Michael R. Hamblin, and Wei R. Chen being the most prolific contributors. The current research focus revolves around novel strategies to enhance antitumor immunity in PDT, including PDT-based dendritic cell vaccines, combination therapies with immune checkpoint inhibitors (ICIs), and the use of nanoparticles for photosensitizer delivery. Furthermore, genes such as CD8A, TNF, CD4, IFNG, CD274, IL6, IL10, CALR, HMGB1, and CTLA4 have been evaluated in the context of PDT-related immunity. PDT not only achieves tumor ablation but also stimulates the immune response, bolstering antitumor immunity. This study highlights the emerging hotspots in PDT-related immune response research and provides valuable insights for future investigations aimed at further enhancing antitumor immunity.
PubMed: 38288443
DOI: 10.3389/fphar.2024.1299253