Immuno oncology

Malignant tumors are often associated with an immunosuppressive tumor microenvironment (TME), rendering most of them resistant to standard-of-care immune checkpoint inhibitors (CPIs). Signal transducer and activator of transcription 3 (STAT3), a ubiquitously expressed transcription factor, has well-defined immunosuppressive functions in several leukocyte populations within the TME. Since the STAT3 protein has been challenging to target using conventional pharmaceutical modalities, we investigated the feasibility of applying systemically delivered RNA interference (RNAi) agents to silence its mRNA directly in tumor-associated immune cells...

The rise of immuno-oncology, including the use of chimeric antigen receptor T-cell (CAR-T) therapy is bringing in a new wave of cancer treatments, particularly in hematologic malignancies. However, data on their adverse events, particularly of the eye, is under-reported. To assess the ocular adverse events associated with the six FDA-approved CAR-T cell therapies, a disproportionality analysis utilizing the FAERS database was conducted from the first quarter of 2017 to the third quarter of 2023, as well as a systematic review of case reports of ocular events following CAR-T cell therapy up to December 20, 2023...

Dendritic cell (DC) vaccination is a promising approach to induce tumor-specific immune responses in cancer patients. Until recently, most DC vaccines were based on in vitro-differentiated monocyte-derived DCs. However, through development of efficient isolation techniques, the use of primary blood dendritic cell subsets has come within reach. Manufacturing of blood-derived DCs has multiple advances over monocytes-derived DCs, including more standardized isolation and culture protocols and shorter production processes...

INTRODUCTION: Immunotherapies have revolutionized cancer treatment, but often fail to produce desirable therapeutic outcomes in all patients. Due to the inter-patient heterogeneity and complexity of the tumor microenvironment, personalized treatment approaches are gaining demand. Researchers have long been using a range of in-vitro assays including 2D models, organoid co-cultures, and cancer-on-a-chip platforms for cancer drug screening. A comparative analysis of these assays with their suitability, high-throughput capacity, and clinical translatability is required for optimal translational use...

BACKGROUND: Immune checkpoint inhibitors (ICIs) have been proposed as the standard first-line and subsequent treatment for metastatic non-small cell lung cancer (NSCLC). This study analyzed whether patients with good lung immune prognostic index (LIPI) have a better response to ICIs and the relationship between immune-related adverse events (irAEs) and response in clinical practice. METHODS: This was an observational, retrospective, single-center study. Patients with stage IV NSCLC between 2016 and 2021 were included in the study...

Immuno-oncology has traditionally focused on conventional MHC-restricted αβ T cells. Yet, unconventional γδ T cells, which kill tumor cells in an MHC-unrestricted manner, display characteristics of effector activity and stemness without exhaustion and are nearly universally observed in human gynecologic malignancies, correlating with improved outcomes. These cells do not have a clear counterpart in mice but are also found in the healthy female reproductive tract. Interventions that modulate their in vivo activity, or cellular therapies utilizing γδ T cells as an allogeneic, "off-the-shelf" platform (e...

BACKGROUND: The study on Head and Neck Squamous Cell Carcinoma (HNSCC), a prevalent and aggressive form of head and neck cancer, focuses on the often-overlooked role of soluble mediators. The objective is to leverage a transcriptome-based risk analysis utilizing soluble mediator-related genes (SMRGs) to provide novel insights into prognosis and immunotherapy efficacy in HNSCC patients. METHODS: We analyzed the expression and prognostic significance of 10,859 SMRGs using 502 HNSCC and 44 normal samples from the TCGA-HNSC cohort in The Cancer Genome Atlas (TCGA)...

While pancreatic ductal adenocarcinomas (PDACs) are addicted to KRAS-activating mutations, inhibitors of downstream KRAS effectors, such as the MEK1/2 kinase inhibitor trametinib, are devoid of therapeutic effects. However, the extensive rewiring of regulatory circuits driven by the attenuation of the KRAS pathway may induce vulnerabilities of therapeutic relevance. An in-depth molecular analysis of the transcriptional and epigenomic alterations occurring in PDAC cells in the initial hours after MEK1/2 inhibition by trametinib unveiled the induction of endogenous retroviruses (ERVs) escaping epigenetic silencing, leading to the production of double-stranded RNAs and the increased expression of interferon (IFN) genes...

No abstract text is available yet for this article.

Innate immunity must be tightly regulated to enable sensitive pathogen detection while averting autoimmunity triggered by pathogen-like host molecules. A hallmark of viral infection, double-stranded RNAs (dsRNAs) are also abundantly encoded in mammalian genomes, necessitating surveillance mechanisms to distinguish 'self' from 'non-self.' ADAR1, an RNA editing enzyme, has emerged as an essential safeguard against dsRNA-induced autoimmunity. By converting adenosines to inosines (A-to-I) in long dsRNAs, ADAR1 covalently marks endogenous dsRNAs, thereby blocking the activation of the cytoplasmic dsRNA sensor MDA5...

Immuno-oncology involves the study of approaches which harness the patient's immune system to fight malignancies. Immuno-oncology, as with every other biomedical and clinical research field as well as clinical operations, is in the midst of technological revolutions, which vastly increase the amount of available data. Recent advances in artificial intelligence and machine learning (AI/ML) have received much attention in terms of their potential to harness available data to improve insights and outcomes in many areas including immuno-oncology...

Despite the large number of existing bispecific antibody (bsAb) formats, the generation of novel bsAbs is still associated with development and bioprocessing challenges. Here, we present RUBY, a novel bispecific antibody format that allows rapid generation of bsAbs that fulfill key development criteria. The RUBYTM format has a 2 + 2 geometry, where two Fab fragments are linked via their light chains to the C-termini of an IgG, and carries mutations for optimal chain pairing. The unique design enables generation of bsAbs with mAb-like attributes...

A patient with bilateral ovarian cancer, peritoneal dissemination, and multiple liver and lung metastases was found with a sudden accumulation of ascites six months after delivery. Chemotherapy was started, but the prognosis was judged to be poor, so immuno-cell therapy was combined with chemotherapy. After multiple cycles of Wilms' tumor antigen 1 (WT1) dendritic cell vaccine therapy and highly activated natural killer (NK) cell therapy, the patient showed a disappearance of ascites and a remarkable reduction of multiple cancers in the whole body...

BACKGROUND: Immuno-oncology has been focused on T cell-centric approaches until the field recently started appreciating the importance of tumor-reactive antibody production by tumor-infiltrating plasma B cells, and the necessity of developing novel therapeutic antibodies for the treatment of different cancers. RECENT FINDINGS: B lymphocytes often infiltrate solid tumors and the extent of B cell infiltration normally correlates with stronger T cell responses while generating humoral responses against malignant progression by producing tumor antigens-reactive antibodies that bind and coat the tumor cells and promote cytotoxic effector mechanisms, reiterating the fact that the adaptive immune system works by coordinated humoral and cellular immune responses...

No abstract text is available yet for this article.

PURPOSE: Immuno-ethanol ablation using an ethanol and immune adjuvant formulation is investigated as a potent immuno-ablation approach that can achieve an enhanced anti-cancer effect in the treatment of hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Ethanol concentration- and exposure time-dependent cellular responses were investigated. Curcumin was combined with ethanol as an immuno-ablation agent. Cellular uptake of curcumin, cancer cell killing, and inflammatory markers of ethanol-curcumin treatment were characterized...

Modeling immuno-oncology by using patient-derived material and immune cell co-cultures can advance our understanding of immune cell tumor targeting in a patient-specific manner, offering leads to improve cellular immunotherapy. However, fully exploiting these living cultures requires analysis of the dynamic cellular features modeled, for which protocols are currently limited. Here, we describe the application of BEHAV3D, a platform that implements multi-color live 3D imaging and computational tools for: (i) analyzing tumor death dynamics at both single-organoid or cell and population levels, (ii) classifying T cell behavior and (iii) producing data-informed 3D images and videos for visual inspection and further insight into obtained results...

The electron transport chain (ETC) couples electron transfer with proton pumping to generate ATP and it also regulates particular innate and adaptive immune cell function. While NLRP3 inflammasome activation was initially linked to reactive oxygen species (ROS) produced from Complexes I and III, recent research suggests that an intact ETC fueling ATP is needed. Complex II may be responsible for Th1 cell proliferation and in some cases, effector cytokine production. Complex III is required for regulatory T (Treg) cell function, while oxidative phosphorylation (OXPHOS) and Complexes I, IV, and V sustain proliferation and antibody production in B lymphocytes, with OXPHOS also being required for B regulatory (Breg) cell function...

No abstract text is available yet for this article.

Assessing cell viability is important in many fields of research. Current optical methods to assess cell viability typically involve fluorescent dyes, which are often less reliable and have poor permeability in primary tissues. Dynamic optical coherence microscopy (dOCM) is an emerging tool that provides label-free contrast reflecting changes in cellular metabolism. In this work, we compare the live contrast obtained from dOCM to viability dyes, and for the first time to our knowledge, demonstrate that dOCM can distinguish live cells from dead cells in murine syngeneic tumors...