scholarly journals Yeast-derived nanoparticles remodel the immunosuppressive microenvironment in tumor and tumor-draining lymph nodes to suppress tumor growth

2022 ◽  
Vol 13 (1) ◽  
Author(s):  
Jialu Xu ◽  
Qingle Ma ◽  
Yue Zhang ◽  
Ziying Fei ◽  
Yifei Sun ◽  
...  
Keyword(s):  
Percolation Model ◽  
Programmed Death ◽  
Functional Orientation ◽  
Draining Lymph Node ◽  
Tumor Draining Lymph Node ◽  
Potential Strategy ◽  
Immunosuppressive Microenvironment ◽  
Draining Lymph Nodes ◽  
Distribution Behavior

AbstractMicrobe-based cancer immunotherapy has recently emerged as a hot topic for cancer treatment. However, serious limitations remain including infection associated side-effect and unsatisfactory outcomes in clinic trials. Here, we fabricate different sizes of nano-formulations derived from yeast cell wall (YCW NPs) by differential centrifugation. The induction of anticancer immunity of our formulations appears to inversely correlate with their size due to the ability to accumulate in tumor-draining lymph node (TDLN). Moreover, we use a percolation model to explain their distribution behavior toward TDLN. The abundance and functional orientation of each effector component are significantly improved not only in the microenvironment in tumor but also in the TDLN following small size YCW NPs treatment. In combination with programmed death-ligand 1 (PD-L1) blockade, we demonstrate anticancer efficiency in melanoma-challenged mice. We delineate potential strategy to target immunosuppressive microenvironment by microbe-based nanoparticles and highlight the role of size effect in microbe-based immune therapeutics.

scholarly journals Tumor-draining lymph node is important for a robust abscopal effect stimulated by radiotherapy

2020 ◽  
Vol 8 (2) ◽  
pp. e000867
Author(s):  
Zachary S Buchwald ◽  
Tahseen H Nasti ◽  
Judong Lee ◽  
Christiane S Eberhardt ◽  
Andres Wieland ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Subset ◽  
Abscopal Effect ◽  
Tumor Irradiation ◽  
Programmed Death ◽  
Draining Lymph Node ◽  
Tumor Draining Lymph Node ◽  
A Site ◽  
Lcmv Infection

BackgroundRadiotherapy (RT) has been shown to stimulate an antitumor immune response in irradiated tumors as well as unirradiated distant sites (abscopal effect). Previous studies have demonstrated a role for the tumor-draining lymph node (LN) in mediating an anti-programmed death-1 (PD-1)/programmed death ligand-1 (PD-L1) stimulated antitumor immune response. Here, we investigated whether the LN is also important in mediating a RT alone stimulated abscopal response.MethodsWe used a subcutaneous modified B16F10 flank tumor model injected bilaterally. Our B16F10 cell line has an inserted viral glycoprotein which facilitated identification of tumor-specific T-cells. RT was directed at one flank tumor alone or one flank tumor and the tumor-draining LN. We evaluated response by tumor growth measurements and flow cytometry of both tumor-infiltrating and LN T-cells.ResultsWe show that local tumor irradiation improves distant tumor control (abscopal effect). Depletion of CD8+ T-cells significantly reduced this abscopal response. We have previously shown, in a chronic lymphocytic choriomeningitis virus (LCMV) infection, that the T-cell proliferative burst following blockade of PD-1/L1 is provided by a ‘stem-like’ CD8+ T-cell subset which then differentiate into terminally differentiated effectors. These terminally differentiated effectors have the potential to kill virally infected or tumor cells following PD-1/L1 blockade. In the chronic LCMV infection, stem-like CD8+ T-cells were found exclusively in secondary lymphoid organs. Similarly, here we found these cells at high frequencies in the tumor-draining LN, but at low frequencies within the tumor. The effect of RT on this T-cell subset in unknown. Interestingly, tumor irradiation stimulated total CD8+ and stem-like CD8+ T-cell proliferation in the LN. When the LN and the tumor were then targeted with RT, the abscopal effect was reduced, and we found a concomitant reduction in the number of total tumor-specific CD8+ T-cells and stem-like CD8+ T-cells in both the irradiated and unirradiated tumor.ConclusionsThese correlative results suggest the tumor-draining LN may be an important mediator of the abscopal effect by serving as a stem-like CD8+ T-cell reservoir, a site for stem-like T-cell expansion, and a site from which they can populate the tumor.

MiRNA-145 and Its Direct Downstream Targets in Digestive System Cancers: A Promising Therapeutic Target

2020 ◽  
Vol 26 ◽  
Author(s):  
Yini Ma ◽  
Xiu Cao ◽  
Guojuan Shi ◽  
Tianlu Shi
Keyword(s):  
Digestive System ◽  
Target Genes ◽  
Malignant Neoplasm ◽  
Vital Role ◽  
Diagnostic Biomarkers ◽  
Cellular Processes ◽  
Promising Therapeutic Target ◽  
Direct Target ◽  
Potential Strategy

: MicroRNAs (miRNAs) play a vital role in the onset and development of many diseases, including cancers. Emerging evidence shows that numerous miRNAs have the potential to be used as diagnostic biomarkers for cancers, and miRNA-based therapy may be a promising therapy for the treatment of malignant neoplasm. MicroRNA-145 (miR-145) has been considered to play certain roles in various cellular processes, such as proliferation, differentiation and apoptosis, via modulating expression of direct target genes. Recent reports show that miR-145 participates in the progression of digestive system cancers, and plays crucial and novel roles for cancer treatment. In this review, we summarize the recent knowledge concerning the function of miR-145 and its direct targets in digestive system cancers. We discuss the potential role of miR-145 as valuable biomarkers for digestive system cancers and how miR-145 regulates these digestive system cancers via different targets to explore the potential strategy of targeting miR-145.

scholarly journals Immune-Related Pancytopenia Induced by Anti-PD-1 Therapy – Interrupt or Continue Treatment – The Role of Immunohistochemical Examination

2019 ◽  
Vol 12 (3) ◽  
pp. 820-828 ◽  
Author(s):  
Bożena Cybulska-Stopa ◽  
Andrzej Gruchała ◽  
Maciej Niemiec
Keyword(s):  
Bone Marrow ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitors ◽  
Death Receptor ◽  
Positive Outcomes ◽  
Hematological Disorders ◽  
Therapeutic Outcomes ◽  
Appropriate Treatment ◽  
Programmed Death

Immune checkpoint inhibitors (ICIs), including anti-cytotoxic T-lymphocyte antigen 4 (anti-CTLA-4) and anti-programmed death receptor-1/ligand-1 (anti-PD-1/anti-PD-L1) caused a breakthrough in oncology and significantly improved therapeutic outcomes in cancer patients. ICIs generate a specific reaction in T cells, directed against antigens on cancer cells, leading to their damage and death. Through similar or the same antigens, activated lymphocytes may also have a cytotoxic effect on healthy cells, causing development of specific adverse effects – so-called immune-related adverse events (irAEs). We present the case report of a 56 year old patient with disseminated melanoma. During treatment with immunotherapy (anti PD-1), neutropenic fever and pancytopenia occurred. Trepanobiopsy of the bone marrow was performed to determine the cause of pancytopenia. Histopathological assessment of bone marrow combined with immunophenotype investigations may explain the cause of hematological disorders occurring in the course of treatment with ICIs, and support the choice of an appropriate treatment, directly translated into positive outcomes.

scholarly journals Cancer Cells Regulate Lymphocyte Recruitment and Leukocyte-Endothelium Interactions in the Tumor-Draining Lymph Node

2005 ◽  
Vol 65 (24) ◽  
pp. 11639-11648 ◽  
Author(s):  
Virginie Carrière ◽  
Renaud Colisson ◽  
Carine Jiguet-Jiglaire ◽  
Elisabeth Bellard ◽  
Gérard Bouche ◽  
...  
Keyword(s):  
Lymph Node ◽  
Cancer Cells ◽  
Draining Lymph Node ◽  
Tumor Draining Lymph Node

scholarly journals Periprocedural Peritonitis Prophylaxis: A Summary of the Microbiology and the Role of Systemic Antimicrobials

2021 ◽  
Vol 7 (2) ◽  
pp. 90-99
Author(s):  
Leon Hsueh ◽  
Susie L. Hu ◽  
Ankur D. Shah
Keyword(s):  
Peritoneal Dialysis ◽  
High Risk ◽  
Antibiotic Prophylaxis ◽  
Catheter Insertion ◽  
Antibiotic Regimen ◽  
Dental Procedures ◽  
Intravenous Antibiotics ◽  
Skin Flora ◽  
Potential Strategy

Background: Peritonitis is a leading complication of peritoneal dialysis (PD). One strategy that the International Society for Peritoneal Dialysis (ISPD) has used to help mitigate the morbidity and mortality associated with peritonitis is through prevention, including antibiotic prophylaxis utilization in high-risk situations. The aim of this study is to summarize our current understanding of postprocedural peritonitis and discuss the existing data behind periprocedural antibiotic prophylaxis, focusing primarily on PD catheter insertion, dental procedures, colonoscopies, upper endoscopies with gastrostomy, and gynecologic procedures. Summary: The ISPD currently recommends intravenous antibiotics prior to PD catheter insertion, colonoscopies, and invasive gynecologic procedures, though prophylaxis has only demonstrated benefit in a prospective, randomized control setting for PD catheter insertion. However, multiple retrospective studies exist that support the use of antibiotic prophylaxis for the other 2 procedures. No specific antibiotic regimen has been established as most optimal to prevent peritonitis for any of the 3 procedures. Antibiotic coverage should include the Enterobacteriaceae family, as well as Gram-positive organisms commonly found on the skin flora for PD catheter insertion, anaerobes for colonoscopies, and common organisms from the urogenital flora in gynecologic procedures. Additionally, the ISPD currently recommends oral amoxicillin prior to dental procedures. There is currently no ISPD recommendation to provide antibiotic prophylaxis prior to an upper endoscopy with or without gastrostomy, though this is a potential area for research. Key Messages: PD patients are at high risk for developing peritonitis after typical procedures. Antibiotic prophylaxis is a potential strategy that the ISPD utilizes to prevent these infections. However, further research needs to be done to determine the optimal antibiotic regimen.

scholarly journals The Role of Yes-Associated Protein (YAP) in Regulating Programmed Death-Ligand 1 (PD-L1) in Thoracic Cancer

Biomedicines ◽  
2018 ◽  
Vol 6 (4) ◽  
pp. 114 ◽  
Author(s):  
Ping-Chih Hsu ◽  
Cheng-Ta Yang ◽  
David Jablons ◽  
Liang You
Keyword(s):  
Immune Responses ◽  
Immune Checkpoint ◽  
T Cell Tolerance ◽  
Programmed Death Ligand 1 ◽  
Programmed Death ◽  
Anti Cancer ◽  
Thoracic Cancer ◽  
Future Work ◽  
Human Nsclc

The programmed death-ligand 1(PD-L1)/PD-1 pathway is an immunological checkpoint in cancer cells. The binding of PD-L1 and PD-1 promotes T-cell tolerance and helps tumor cells escape from host immunity. Immunotherapy targeting the PD-L1/PD-1 axis has been developed as an anti-cancer therapy and used in treating advanced human non-small cell lung cancer (NSCLC) and malignant pleural mesothelioma (MPM). Yes-associated protein (YAP) is a key mediator of the Hippo/YAP signaling pathway, and plays important roles in promoting cancer development, drug resistance and metastasis in human NSCLC and MPM. YAP has been suggested as a new therapeutic target in NSCLC and MPM. The role of YAP in regulating tumor immunity such as PD-L1 expression has just begun to be explored, and the correlation between YAP-induced tumorigenesis and host anti-tumor immune responses is not well known. Here, we review recent studies investigating the correlation between YAP and PD-L1 and demonstrating the mechanism by which YAP regulates PD-L1 expression in human NSCLC and MPM. Future work should focus on the interactions between Hippo/YAP signaling pathways and the immune checkpoint PD-L1/PD-1 pathway. The development of new synergistic drugs for immune checkpoint PD-L1/PD-1 blockade in NSCLC and MPM is warranted.

scholarly journals Protective Role of Programmed Death 1 Ligand 1 (PD-L1)in Nonobese Diabetic Mice: The Paradox in Transgenic Models

Diabetes ◽  
2008 ◽  
Vol 57 (7) ◽  
pp. 1861-1869 ◽  
Author(s):  
C.-J. Wang ◽  
F.-C. Chou ◽  
C.-H. Chu ◽  
J.-C. Wu ◽  
S.-H. Lin ◽  
...  
Keyword(s):  
Protective Role ◽  
Diabetic Mice ◽  
Transgenic Models ◽  
Nonobese Diabetic ◽  
Programmed Death ◽  
Programmed Death 1 ◽  
Nonobese Diabetic Mice
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