Immune cancer

The advancement of mRNA-based immunotherapies for cancer is highly dependent on the effective delivery of RNA payloads using ionizable lipid nanoparticles (LNPs). However, the clinical application of these therapies is hindered by variable mRNA expression among different cancer types and the risk of systemic toxicity. The transient expression profile of mRNA further complicates this issue, necessitating frequent dosing and thus increasing the potential for adverse effects. Addressing these challenges, we utilized a high-throughput combinatorial method to synthesize and screen LNPs that efficiently deliver circular RNA (circRNA) to lung tumors...

The intricate tumor microenvironment in triple-negative breast cancer (TNBC) hampers chemotherapy and immunotherapy efficacy due to dense extracellular matrix (ECM) by tumor-associated fibroblasts (TAFs). Nanoparticle-based therapies, especially "all in one" nanoparticles, have shown great potential in combined drug delivery strategies to reshape the tumor microenvironment and enhance therapeutic efficiency. However, these "all in one" nanoparticles suffer from limitations in targeting different target cells, uncontrollable dosing ratio, and disregarding the impact of delivery schedules...

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...

Chemotherapeutics, radiation, targeted therapeutics and immunotherapeutics each demonstrate clinical benefits for a small subset of patients with solid malignancies. Immune cells infiltrating the tumor and the surrounding stroma play a critical role in shaping cancer progression and modulating therapy response. They do this by interacting with the other cellular and molecular components of the tumor microenvironment (TME). Spatial multi-OMICs technologies are rapidly evolving. Currently, such technologies allow high-throughput RNA and protein profiling and retain geographical information about the TME cellular architecture and the functional phenotype of tumor, immune and stromal cells...

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with limited therapeutic options. Interleukin-1 receptor type 2 (IL1R2) promotes breast tumor-initiating cell (BTIC) self-renewal and tumor growth in TNBC, indicating that targeting it could improve patient treatment. Here, we observed that IL1R2 blockade strongly attenuated macrophage recruitment and the polarization of tumor-associated macrophages (TAMs) to inhibit BTIC self-renewal and CD8+ T cell exhaustion, which resulted in reduced tumor burden and prolonged survival in TNBC mouse models...

BACKGROUND: Patients with gastric cancer respond poorly to immunotherapy. There are still unknowns about the biomarkers associated with immunotherapy sensitivity and their underlying molecular mechanisms. METHODS: Gene expression data for gastric cancer were gathered from TCGA and GEO databases. DEGs associated with immunotherapy response came from ICBatlas. KEGG and GO analyses investigated pathways. Hub genes identification employed multiple machine algorithms...

BACKGROUND: CESC is the second most commonly diagnosed gynecological malignancy. Given the pivotal involvement of metabolism-related genes (MRGs) in the etiology of multiple tumors, our investigation aims to devise a prognostic risk signature rooted in cancer stemness and metabolism. METHODS: The stemness index based on mRNA expression (mRNAsi) of samples from the TCGA dataset was computed using the One-class logistic regression (OCLR) algorithm. Furthermore, potential metabolism-related genes related to mRNAsi were identified through weighted gene co-expression network analysis (WGCNA)...

Evolutionary theory predicts that accumulation of deleterious mutations in asexually reproducing organisms should lead to genomic decay. Clonally reproducing cell lines, i.e., transmissible cancers, when cells are transmitted as allografts/xenografts, break these rules, and survive for centuries and millennia. The currently known 11 transmissible cancer lineages occur in dogs (Canine Venereal Tumour Disease, CTVT), in Tasmanian devils (Devil Facial Tumour Diseases, DFT 1 and DFT2) and in bivalves (bivalve transmissible neoplasia, BTN)...

Accumulating evidence suggests that lymphangiogenesis plays a crucial role in lymphatic metastasis, leading to tumor immune tolerance. However, the specific mechanism remains unclear. In this study, miR-431-5p was markedly downregulated in both gastric cancer (GC) tissues and plasma exosomes, and its expression were correlated negatively with LN metastasis and poor prognosis. Mechanistically, miR-431-5p weakens the TGF-β1/SMAD2/3 signaling pathway by targeting ZEB1, thereby suppressing the secretion of VEGF-A and ANG2, which in turn hinders angiogenesis, lymphangiogenesis, and lymph node (LN) metastasis in GC...

PURPOSE: Increased expression of leukocyte immunoglobulin-like receptor subfamily B member 2 (LILRB2) is associated with immune evasion in breast cancer (BC). The aim of this study to elucidate the role of LILRB2 in BC progression. METHODS: LILRB2 expression in tumor tissues was detected by immunohistochemical staining. Human leukocyte antigen A (HLA-A) expression in BC cells was detected by Western blotting, and HLA-A ubiquitination was detected by immunoprecipitation and histidine pulldown assay...

PURPOSE: The receptor-interacting protein kinase (RIPK4) has an oncogenic function in melanoma, regulates NF-κB and Wnt/β-catenin pathways, and is sensitive to the BRAF inhibitors: vemurafenib and dabrafenib which lead to its decreased level. As its role in melanoma remains not fully understood, we examined the effects of its downregulation on the transcriptomic profile of melanoma. METHODS: Applying RNA-seq, we revealed global alterations in the transcriptome of WM266...

Carotenoids are the natural pigments available in nature and exhibit different colors such as yellow, red, and orange. These are a class of phytonutrients that have anti-cancer, anti-inflammatory, anti-oxidant, immune-modulatory, and anti-aging properties. These were used in food, pharmaceutical, nutraceutical, and cosmetic industries. They are divided into two classes: carotenes and xanthophylls. The carotenes are non-oxygenated derivatives and xanthophylls are oxygenated derivatives. The major source of carotenoids are vegetables, fruits, and tissues...

Myeloid neoplasms are a group of bone marrow diseases distinguished by disruptions in the molecular pathways that regulate the balance between hematopoietic stem cell (HSC) self-renewal and the generation of specialized cells. Cytokines and chemokines, two important components of the inflammatory process, also influence hematological differentiation. In this scenario, immunological dysregulation plays a pivotal role in the pathogenesis of bone marrow neoplasms. The STING pathway recognizes DNA fragments in the cell cytoplasm and triggers an immune response by type I interferons...

Chimeric Antigen Receptor (CAR) based therapies are becoming increasingly important in treating patients. CAR-T cells have been shown to be highly effective in the treatment of hematological malignancies. However, harmful therapeutic barriers have been identified, such as the potential for graft-versus-host disease (GVHD), neurotoxicity, and cytokine release syndrome (CRS). As a result, CAR NK-cell therapy is expected to be a new therapeutic option. NK cells act as cytotoxic lymphocytes, supporting the innate immune response against autoimmune diseases and cancer cells by precisely detecting and eliminating malignant cells...

Inactivated COVID-19 vaccines data in immunocompromised individuals are scarce. This trial assessed the immunogenicity of two CoronaVac doses and additional BNT162b2 mRNA vaccine doses in immunocompromised (IC) and immunocompetent (H) individuals. Adults with solid organ transplant (SOT), hematopoietic stem cell transplant, cancer, inborn immunity errors or rheumatic diseases were included in the IC group. Immunocompetent adults were used as control group for comparison. Participants received two CoronaVac doses within a 28-day interval...

Conditions related to the acquired immune deficiency syndrome (AIDS) are still a significant cause of morbidity and mortality among people living with HIV (PLHIV). Longer survival in this population were reported to increase the risk of developing noncommunicable chronic diseases (NCDs). This study aimed to estimate the survival and causes of death according to age group and sex among PLHIV monitored at two referral centers in the Northeastern Brazil. This is a prospective, retrospective cohort with death records from 2007 to 2018, based on a database that registers causes of death using the International Classification of Disease (ICD-10), which were subsequently coded following the Coding Causes of Death in HIV (CoDe)...

DNA damage is a prevalent phenomenon in the context of cancer progression. Evidence suggests that DNA damage responses (DDR) are pivotal in overcoming tumor immune evasion. Alternatively, traditional radiotherapy and chemotherapy operate by inducing DNA damage, consequently stimulating the immune system to target tumors. The intricate interplay between signaling pathways involved in DDR and immune activation underscores the significance of considering both factors in developing improved immunotherapies. By delving deeper into the mechanisms underlying immune activation brought on by DNA damage, it becomes possible to identify novel treatment approaches that boost the anticancer immune response while minimizing undesirable side effects...

Cycling myeloid cells (CMCs) are often detected from various tissues using single-cell RNA sequencing (scRNA-seq) datasets, however, their research value was not noticed before. For the first time, our study preliminarily revealed the origin, differentiation, and roles of CMCs in physiological processes. Particularly, subgroup a of cycling myeloid cells (aCMCs) were conclusively identified as belonging to a specific cell type. In an active state, aCMCs rapidly proliferate during the early stages of an embryonic development...

OBJECTIVE: Carcinoma ex-pleomorphic adenoma (CEXPA) represents a malignant transformation from a recurrent or primary pleomorphic adenoma (PA), and the immune response may be essential in this process. Therefore, in this study, we aimed to identify and quantify subpopulations of dendritic cells (DCs) in CEXPA, residual PA in CEXPA (rPA), and PA. MATERIALS AND METHODS: A multicenter study was performed collecting salivary gland tumor (SGT) samples from three Oral and Maxillofacial Pathology Centers...

OBJECTIVE: This study (CRD42023464989) aimed to explore the effects of pre-operation immunonutrition on safety and immune related factors in colorectal cancer patients undergoing surgery. METHODS: We systematically searched PubMed, Embase, and Wanfang databases to collect all clinical randomized controlled trials of the application of pre-operation immunonutrition for patients with colorectal cancer, published until July 2023. The primary outcomes were safety and immune related factors...