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JOURNAL ARTICLE
Joseph Markowitz, Michael Shamblott, Andrew S Brohl, Amod A Sarnaik, Zeynep Eroglu, Nikhil I Khushalani, Christopher W Dukes, Alejandra Chamizo, Marina Bastawrous, Edward T Garcia, Ashraf Delhawi, Pei-Ling Chen, Deanryan B De Aquino, Vernon K Sondak, Ahmad A Tarhini, Youngchul Kim, Patricia Lawman, Shari Pilon-Thomas
IFx-Hu2.0 was designed to encode part of the Emm55 protein contained within a plasmid in a formulation intended for transfection into mammalian cells. IFx-Hu2.0 promotes both adaptive and innate immune responses in animal studies. Furthermore, previous studies have demonstrated safety/efficacy in equine, canine, and murine species. We present the first-in-human study of IFx-Hu2.0, administered by intralesional injection into melanoma tumors of seven patients with stage III/IV unresectable melanoma. No dose-limiting toxicities attributable to IFx-Hu2...
April 24, 2024: Molecular Cancer Therapeutics
#2
REVIEW
Sulieman Ibraheem Shelash Al-Hawary, Yasir Qasim Almajidi, Pooja Bansal, Irfan Ahmad, Harpreet Kaur, Ahmed Hjazi, Mahamedha Deorari, Ahmed Hussein Zwamel, Hamza Fadhel Hamzah, Bahira Abdulrazzaq Mohammed
Tumor-mediated immunosuppression is a fundamental obstacle to the development of dendritic cell (DC)-based cancer vaccines, which despite their ability to stimulate host anti-tumor CD8 T cell immunity, have not been able to generate meaningful therapeutic responses. Exosomes are inactive membrane vesicles that are nanoscale in size and are produced by the endocytic pathway. They are essential for intercellular communication. Additionally, DC-derived exosomes (DEXs) contained MHC class I/II (MHCI/II), which is frequently complexed with antigens and co-stimulatory molecules and is therefore able to prime CD4 and CD8 T cells that are specific to particular antigens...
April 6, 2024: Pathology, Research and Practice
#3
JOURNAL ARTICLE
Nilanjan Ganguly, Tapasi Das, Avishek Bhuniya, Ipsita Guha, Mohona Chakravarti, Sukanya Dhar, Anirban Sarkar, Saurav Bera, Jesmita Dhar, Shayani Dasgupta, Akata Saha, Tithi Ghosh, Juhina Das, Ugir Hossain Sk, Saptak Banerjee, Subrata Laskar, Anamika Bose, Rathindranath Baral
BACKGROUND: A water-soluble ingredient of mature leaves of the tropical mahogany 'Neem' (Azadirachta indica), was identified as glycoprotein, thus being named as 'Neem Leaf Glycoprotein' (NLGP). This non-toxic leaf-component regressed cancerous murine tumors (melanoma, carcinoma, sarcoma) recurrently in different experimental circumstances by boosting prime antitumor immune attributes. Such antitumor immunomodulation, aid cytotoxic T cell (Tc )-based annihilation of tumor cells. This study focused on identifying and characterizing the signaling gateway that initiate this systemic immunomodulation...
April 23, 2024: Cell Communication and Signaling: CCS
#4
REVIEW
Andrea Francesca M Salvador, Nora Abduljawad, Jonathan Kipnis
Since its recent discovery, the meningeal lymphatic system has reshaped our understanding of central nervous system (CNS) fluid exchange, waste clearance, immune cell trafficking, and immune privilege. Meningeal lymphatics have also been demonstrated to functionally modify the outcome of neurological disorders and their responses to treatment, including brain tumors, inflammatory diseases such as multiple sclerosis, CNS injuries, and neurodegenerative disorders such as Alzheimer's and Parkinson's diseases. In this review, we discuss recent evidence of the contribution of meningeal lymphatics to neurological diseases, as well as the available experimental methods for manipulating meningeal lymphatics in these conditions...
April 22, 2024: Annual Review of Neuroscience
#5
JOURNAL ARTICLE
C J Pantoja, H Li, J Rodante, A Keel, A V Sorokin, A Svedbom, H L Teague, M Stahle, N N Mehta, M P Playford
BACKGROUND: Beta-defensins (BDs) are antimicrobial peptides secreted upon epithelial injury. Both chemotactic and antimicrobial properties of BDs function as initial steps in host defense and prime the adaptive immune system in the body. Psoriasis, a chronic immune-mediated inflammatory disease, has both visible cutaneous manifestations as well as known associations with higher incidence of cardiometabolic complications and vascular inflammation. OBJECTIVES: We aimed to investigate the circulating expression of beta-defensin-2 (BD2) in psoriasis at baseline compared to control subjects, along with changes in BD2 levels following biologic treatment at one-year...
March 2024: JEADV Clin Pract
#6
Emily F Higgs, Thomas F Gajewski
Previous work has shown that innate immune sensing of tumors involves the host STING pathway, which leads to IFN-β production, dendritic cell (DC) activation, and T cell priming against tumor antigens. This observation has led to the development of STING agonists as a potential cancer therapeutic. However, despite promising results in mouse studies using transplantable tumor models, clinical testing of STING agonists has shown activity in only a minority of patients. Thus, further study of innate immune pathways in anti-tumor immunity is paramount...
April 12, 2024: bioRxiv
#7
JOURNAL ARTICLE
Ting Fu, Kofi Amoah, Tracey W Chan, Jae Hoon Bahn, Jae-Hyung Lee, Sari Terrazas, Rockie Chong, Sriram Kosuri, Xinshu Xiao
Understanding the function of rare non-coding variants represents a significant challenge. Using MapUTR, a screening method, we studied the function of rare 3' UTR variants affecting mRNA abundance post-transcriptionally. Among 17,301 rare gnomAD variants, an average of 24.5% were functional, with 70% in cancer-related genes, many in critical cancer pathways. This observation motivated an interrogation of 11,929 somatic mutations, uncovering 3928 (33%) functional mutations in 155 cancer driver genes. Functional MapUTR variants were enriched in microRNA- or protein-binding sites and may underlie outlier gene expression in tumors...
April 18, 2024: Nature Communications
#8
JOURNAL ARTICLE
Wei Yang, Jianwei Cao, Sichen Di, Wenjin Chen, Hui Cheng, Hongze Ren, Yujie Xie, Liang Chen, Meihua Yu, Yu Chen, Xingang Cui
Inherently immunogenic materials offer enormous prospects in enhancing vaccine efficacy. However, the understanding and improving material adjuvanticity remain elusive. Herein how the structural presentation of immunopotentiators in a material governs the dynamic dialogue between innate and adaptive immunity for enhanced cancer vaccination is reported. The immunopotentiator manganese into six differing structures that resemble the architectures of two types of pathogens (spherical viruses or rod-like bacteria) is precisely manipulated...
April 17, 2024: Advanced Materials
#9
JOURNAL ARTICLE
Junseok Lee, Keon-Il Im, Sojin Gil, Hyemin Na, Gi-June Min, Nayoun Kim, Seok-Goo Cho
Immune checkpoint inhibitors have revolutionized anti-tumor therapy, notably improving treatment responses in various tumors. However, many patients remain non-responsive and do not experience benefits. Given that Toll-like receptors (TLRs) can counteract tumor immune tolerance by stimulating both innate and adaptive immune responses, TLR agonists are being explored as potential immune adjuvants for cancer treatment. In this study, we assessed the potential of enhancing the efficacy of immune checkpoint inhibitors by activating innate immunity with a TLR5 agonist...
April 17, 2024: Cancer Immunology, Immunotherapy: CII
#10
JOURNAL ARTICLE
Rachanaa Raja, Rajamanikandan Sundararaj, Ruckmani Kandasamy
The reciprocal suppression of an RNA-binding protein LIN28 (human abnormal cell lineage 28) and miRNA Let-7 (Lethal 7) is considered to have a prime role in hepatocellular carcinoma (HCC). Though targeting this inhibition interaction is effective for therapeutics, it causes other unfavorable effects on glucose metabolism and increased insulin resistance. Hence, this study aims to identify small molecules targeting Lin28/let-7 interaction along with additional potency to improve insulin sensitivity. Of 22,14,996 small molecules screened by high throughput virtual screening, 6 molecules, namely 41354, 1558, 12437, 23837, 15710, and 8319 were able to block the LIN28 interaction with let-7 and increase the insulin sensitivity via interacting with PPARγ (peroxisome proliferator-activated receptors γ)...
April 17, 2024: Medical Oncology
#11
JOURNAL ARTICLE
Nahide Yildirim, Lakshmi Sarojam, Victoria M Smith, Nadja M Pieper, Marius Anders, Ross A Jackson, Dominik C Fuhrmann, Vinzenz Särchen, Daniela Brücher, Andreas Weigert, Martin J S Dyer, Meike Vogler
BH3-mimetics represent promising anti-cancer agents in tumors that rely on the anti-apoptotic function of B-Cell Lymphoma 2 (BCL2) proteins, particularly in leukemia and lymphoma cells primed for apoptosis. Mechanistically, BH3-mimetics may displace pro-apoptotic binding partners thus inducing BAX/BAK-mediated mitochondrial permeabilization followed by cytochrome c release, activation of the caspase cascade and apoptosis. Here, we describe a novel mode of caspase-independent cell death (CICD) induced by BH3-mimetics in a subset of diffuse large B-cell lymphoma (DLBCL) cells...
April 15, 2024: Cell Death & Disease
#12
Emily M Carvalho, Erika A Ding, Atul Saha, Anna Weldy, Peter-James H Zushin, Andreas Stahl, Manish K Aghi, Sanjay Kumar
Hyaluronic acid (HA), the primary component of brain extracellular matrix, is increasingly used to model neuropathological processes, including glioblastoma (GBM) tumor invasion. While elastic hydrogels based on crosslinked low-molecular-weight (LMW) HA are widely exploited for this purpose and have proven valuable for discovery and screening, brain tissue is both viscoelastic and rich in high-MW (HMW) HA, and it remains unclear how these differences influence invasion. To address this question, hydrogels comprised of either HMW (1...
April 6, 2024: bioRxiv
#13
JOURNAL ARTICLE
Christopher Hackenbruch, Jens Bauer, Jonas S Heitmann, Yacine Maringer, Annika Nelde, Monika Denk, Lisa Zieschang, Christine Kammer, Birgit Federmann, Susanne Jung, Peter Martus, Nisar P Malek, Konstantin Nikolaou, Helmut R Salih, Michael Bitzer, Juliane S Walz
UNLABELLED: The DNAJB1-PRKACA fusion transcript was identified as the oncogenic driver of tumor pathogenesis in fibrolamellar hepatocellular carcinoma (FL-HCC), also known as fibrolamellar carcinoma (FLC), as well as in other tumor entities, thus representing a broad target for novel treatment in multiple cancer entities. FL-HCC is a rare primary liver tumor with a 5-year survival rate of only 45%, which typically affects young patients with no underlying primary liver disease. Surgical resection is the only curative treatment option if no metastases are present at diagnosis...
2024: Frontiers in Oncology
#14
REVIEW
Charles M Bowen, Krishna M Sinha, Eduardo Vilar
The coming of age for cancer treatment has experienced exponential growth in the last decade with the addition of immunotherapy as the fourth pillar to the fundamentals of cancer treatment-chemotherapy, surgery, and radiation-taking oncology to an astounding new frontier. In this time, rapid developments in computational biology coupled with immunology have led to the exploration of priming the host immune system through vaccination to prevent and treat certain subsets of cancer such as melanoma and hereditary colorectal cancer...
May 2024: Clinics in Colon and Rectal Surgery
#15
REVIEW
Sarah B Gitto, Chibuike J N Ihewulezi, Daniel J Powell
Although ovarian cancer patients typically respond to standard of care therapies, including chemotherapy and DNA repair inhibitors, the majority of tumors recur highlighting the need for alternative therapies. Ovarian cancer is an immunogenic cancer in which the accumulation of tumor infiltrating lymphocytes (TILs), particularly T cells, is associated with better patient outcome. Thus, harnessing the immune system through passive administration of T cells, a process called adoptive cell therapy (ACT), is a promising therapeutic option for the treatment of ovarian cancer...
April 10, 2024: Gynecologic Oncology
#16
JOURNAL ARTICLE
Shihao Wang, Lifeng Liu, Limin Tian, Pengcheng Xu, Shixuan Li, Lixin Hu, Yanming Xia, Yang Ding, Jian Wang, Suxin Li
Combining immune checkpoint blockade with chemotherapy through nanotechnology is promising in terms of safety and efficacy. However, the distinct subcellular distribution of each ingredient's action site makes it challenging to acquire an optimal synergism. Herein, a dual-pH responsive hybrid polymeric micelle system, HNP(αPDL16.9 , Dox5.3 ), is constructed as a proof-of-concept for the spatial cooperativity in chemo-immunotherapy. HNP retains the inherent pH-transition of each polymer, with stepwise disassembly under discrete pH thresholds...
April 11, 2024: Advanced Materials
#17
JOURNAL ARTICLE
Elysse C Filipe, Sipiththa Velayuthar, Ashleigh Philp, Max Nobis, Sharissa L Latham, Amelia L Parker, Kendelle J Murphy, Kaitlin Wyllie, Gretel S Major, Osvaldo Contreras, Ellie T Y Mok, Ronaldo F Enriquez, Suzanne McGowan, Kristen Feher, Lake-Ee Quek, Sarah E Hancock, Michelle Yam, Emmi Tran, Yordanos F I Setargew, Joanna N Skhinas, Jessica L Chitty, Monica Phimmachanh, Jeremy Z R Han, Antonia L Cadell, Michael Papanicolaou, Hadi Mahmodi, Beata Kiedik, Simon Junankar, Samuel E Ross, Natasha Lam, Rhiannon Coulson, Jessica Yang, Anaiis Zaratzian, Andrew M Da Silva, Michael Tayao, Ian L Chin, Aurélie Cazet, Maya Kansara, Davendra Segara, Andrew Parker, Andrew J Hoy, Richard P Harvey, Ozren Bogdanovic, Paul Timpson, David R Croucher, Elgene Lim, Alexander Swarbrick, Jeff Holst, Nigel Turner, Yu Suk Choi, Irina V Kabakova, Andrew Philp, Thomas R Cox
In recent decades, the role of tumor biomechanics on cancer cell behavior at the primary site has been increasingly appreciated. However, the effect of primary tumor biomechanics on the latter stages of the metastatic cascade, such as metastatic seeding of secondary sites and outgrowth remains underappreciated. This work sought to address this in the context of triple negative breast cancer (TNBC), a cancer type known to aggressively disseminate at all stages of disease progression. Using mechanically tuneable model systems, mimicking the range of stiffness's typically found within breast tumors, it is found that, contrary to expectations, cancer cells exposed to softer microenvironments are more able to colonize secondary tissues...
April 11, 2024: Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
#18
JOURNAL ARTICLE
Michihisa Kono, Shin Saito, Masahiro Rokugo, Ann Marie Egloff, Ravindra Uppaluri
OBJECTIVES: Understanding head and neck tissue specific immune responses is important for elucidating immunotherapy resistance mechanisms to head and neck squamous cell carcinoma (HNSCC). In this study, we aimed to investigate HNSCC-specific immune response differences between oral and subcutaneous flank tumor transplantation in preclinical models. MATERIALS AND METHODS: The MOC1 syngeneic mouse oral carcinoma cell line or versions expressing either the H2Kb-restricted SIINFEKL peptide from ovalbumin (MOC1OVA) or ZsGreen (MOC1ZsGreen) were inoculated into mouse oral mucosa (buccal space) or subcutaneous flank and compared for immune cell kinetics in tumors and tumor-draining lymph nodes (TDLNs) and for anti-PD1 response...
April 9, 2024: Oral Oncology
#19
JOURNAL ARTICLE
Connie S Chamberlain, Archana Prabahar, John A Kink, Erika Mueller, Yiyao Li, Stephanie Yopp, Christian M Capitini, Peiman Hematti, William L Murphy, Ray Vanderby, Peng Jiang
Although mesenchymal stromal cell (MSC) based therapies hold promise in regenerative medicine, their clinical application remains challenging due to issues such as immunocompatibility. MSC-derived exosomes are a promising off-the-shelf therapy for promoting wound healing in a cell-free manner. However, the potential to customize the content of MSC-exosomes, and understanding how such modifications influence exosome effects on tissue regeneration remain underexplored. In this study, we used an in vitro system to compare the priming of human MSCs by two inflammatory inducers TNF-α and CRX-527 (a highly potent synthetic TLR4 agonist that can be used as a vaccine adjuvant or to induce anti-tumor immunity) on exosome molecular cargo, as well as on an in vivo rat ligament injury model to validate exosome potency...
April 10, 2024: Stem Cells
#20
JOURNAL ARTICLE
Katherine H Griffin, Rachel R Mizenko, Vishalakshi Arun, Randy P Carney, J Kent Leach
Metastasis is the principal factor in poor prognosis for individuals with osteosarcoma (OS). Understanding the events that lead to metastasis is critical to develop better interventions for this disease. Alveolar macrophages are potentially involved in priming the lung microenvironment for OS metastasis, yet the mechanisms involved in this process remain unclear. Since extracellular vesicles (EVs) are a known actor in primary tumor development, their potential role in OS metastagenesis through macrophage modulation is explored here...
April 10, 2024: Advanced biology
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