A scalable, spin-free approach to generate enhanced induced pluripotent stem cell-derived natural killer cells for cancer immunotherapy.

Natural killer (NK) cells play a vital role in innate immunity and show great promise in cancer immunotherapy. Traditional sources of NK cells, such as the peripheral blood, are limited by availability and donor variability. In addition, in vitro expansion can lead to functional exhaustion and gene editing challenges.

The Current Molecular and Cellular Landscape of Chronic Obstructive Pulmonary Disease (COPD): A Review of Therapies and Efforts towards Personalized Treatment.

Chronic obstructive pulmonary disease (COPD) ranks as the third leading cause of global illness and mortality. It is commonly triggered by exposure to respiratory irritants like cigarette smoke or biofuel pollutants. This multifaceted condition manifests through an array of symptoms and lung irregularities, characterized by chronic inflammation and reduced lung function.

The immune checkpoint TIGIT is upregulated on T cells during bacterial infection and is a potential target for immunotherapy.

Antibiotic resistance is a major public health threat, and alternatives to antibiotic therapy are urgently needed. Immunotherapy, particularly the blockade of inhibitory immune checkpoints, is a leading treatment option in cancer and autoimmunity. In this study, we used a murine model of Salmonella Typhimurium infection to investigate whether immune checkpoint blockade could be applied to bacterial infection.

TGF-β signalling limits effector function capacity of NK cell anti-tumour immunity in human bladder cancer.

Background: Natural killer (NK) cells are important innate immunity players and have unique abilities to recognize and eliminate cancer cells, particularly in settings of antibody-opsonization and antibody-dependant cellular cytotoxicity (ADCC). However, NK cell-based responses in bladder cancers to therapeutic antibodies are typically immunosuppressed, and these immunosuppressive mechanisms are largely unknown.

Methods: Single cell RNA sequencing (scRNA-seq) and high-dimensional flow cytometry were used to investigate the phenotype of tumour-infiltrating NK cells in patients with bladder cancer.

Highlight of 2023: Unlocking the therapeutic potential of natural killer cells-advances in adaptive functions, cellular engineering and immunotherapy.

Natural killer (NK) cells possess potent cytotoxicity against infected and cancerous cells and hold promise in the development of new immunotherapies. This article for the Highlights of 2023 Series focuses on current advances in NK cell biology in cancerous and infectious settings and highlights opportunities for therapeutic interventions, including engineered NK cell therapies and advancements in feeder cell technologies.

Exploring NK cell receptor dynamics in paediatric leukaemias: implications for immunotherapy and prognosis.

Objectives: Immunotherapies targeting natural killer (NK) cell receptors have shown promise against leukaemia. Unfortunately, cancer immunosuppressive mechanisms that alter NK cell phenotype prevent such approaches from being successful. The study utilises advanced cytometry to examine how cancer immunosuppressive pathways affect NK cell phenotypic changes in clinical samples.

In situ single-cell profiling sheds light on IFI27 localisation during SARS-CoV-2 infection.

The utilization of single-cell resolved spatial transcriptomics to delineate immune responses during SARS-CoV-2 infection was able to identify M1 macrophages to have elevated expression of IFI27 in areas of infection.

Leveraging spatial omics for the development of precision sarcoma treatments.

Sarcomas are rare and heterogeneous cancers that arise from bone or soft tissue, and are the second most prevalent solid cancer in children and adolescents. Owing to the complex nature of pediatric sarcomas, the development of therapeutics for pediatric sarcoma has seen little progress in the past decades. Existing treatments are largely limited to chemotherapy, radiation, and surgery.

IKAROS and AIOLOS directly regulate AP-1 transcriptional complexes and are essential for NK cell development.

Ikaros transcription factors are essential for adaptive lymphocyte function, yet their role in innate lymphopoiesis is unknown. Using conditional genetic inactivation, we show that Ikzf1/Ikaros is essential for normal natural killer (NK) cell lymphopoiesis and IKZF1 directly represses Cish, a negative regulator of interleukin-15 receptor resulting in impaired interleukin-15 receptor signaling. Both Bcl2l11 and BIM levels, and intrinsic apoptosis were increased in Ikzf1-null NK cells, which in part accounts for NK lymphopenia as both were restored to normal levels when Ikzf1 and Bcl2l11 were co-deleted.

Molecular mechanisms of tumour necrosis factor signalling via TNF receptor 1 and TNF receptor 2 in the tumour microenvironment.

Tumour necrosis factor (TNF) is a primary mediator of inflammatory processes by facilitating cell death, immune cell activation and triggering of inflammation. In the cancer context, research has revealed TNF as a multifaceted cytokine that can be both pro- or anti-tumorigenic depending on what context is observed. We explore the plethora of ways that TNF and its receptors manipulate the functional and phenotypic characteristics in the tumour microenvironment (TME) on both tumour cells and immune cells, promoting either tumour elimination or progression.

Development of Physiologically Relevant Skin Organoids from Human Induced Pluripotent Stem Cells.

The development of skin organs for studying developmental pathways, modeling diseases, or regenerative medicine purposes is a major endeavor in the field. Human induced pluripotent stem cells (hiPSCs) are successfully used to derive skin cells, but the field is still far from meeting the goal of creating skin containing appendages, such as hair follicles and sweat glands. Here, the goal is to generate skin organoids (SKOs) from human skin fibroblast or placental CD34+ cell-derived hiPSCs.

A robust platform for integrative spatial multi-omics analysis to map immune responses to SARS-CoV-2 infection in lung tissues.

The SARS-CoV-2 (COVID-19) virus has caused a devastating global pandemic of respiratory illness. To understand viral pathogenesis, methods are available for studying dissociated cells in blood, nasal samples, bronchoalveolar lavage fluid and similar, but a robust platform for deep tissue characterization of molecular and cellular responses to virus infection in the lungs is still lacking. We developed an innovative spatial multi-omics platform to investigate COVID-19-infected lung tissues.

transcription is an early predictor for COVID-19 outcomes, a multi-cohort observational study.

Purpose: Robust biomarkers that predict disease outcomes amongst COVID-19 patients are necessary for both patient triage and resource prioritisation. Numerous candidate biomarkers have been proposed for COVID-19. However, at present, there is no consensus on the best diagnostic approach to predict outcomes in infected patients.

CIS controls the functional polarization of GM-CSF-derived macrophages.

The cytokine granulocyte-macrophage-colony stimulating factor (GM-CSF) possesses the capacity to differentiate monocytes into macrophages (MØs) with opposing functions, namely, proinflammatory M1-like MØs and immunosuppressive M2-like MØs. Despite the importance of these opposing biological outcomes, the intrinsic mechanism that regulates the functional polarization of MØs under GM-CSF signaling remains elusive. Here, we showed that GM-CSF-induced MØ polarization resulted in the expression of cytokine-inducible SH2-containing protein (CIS) and that CIS deficiency skewed the differentiation of monocytes toward immunosuppressive M2-like MØs.

Weaponizing natural killer cells for solid cancer immunotherapy.

Enhancing natural killer (NK) cell-based innate immunity has become a promising strategy for immunotherapy against hard-to-cure solid cancers. Monoclonal antibody (mAb) therapy has been used to activate NK-cell-mediated antibody-dependent cellular cytotoxicity (ADCC) towards solid cancers. Cancer cells, however, can subvert immunosurveillance using multiple immunosuppressive mechanisms, which may hamper NK cell ADCC.

The cancer cell-derived extracellular vesicle glycocode in immunoevasion.

Recent evidence suggests that cancer cell-derived extracellular vesicles might facilitate immunoevasion. Glycans are known to play a key role in immunomodulation, especially when tethered to biological membranes. However, the extracellular vesicle glycocode in cancer immunoevasion remains a largely unexplored area with promising potential for new putative diagnostic and therapeutic applications.

Transcriptomic profiling of cardiac tissues from SARS-CoV-2 patients identifies DNA damage.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is known to present with pulmonary and extra-pulmonary organ complications. In comparison with the 2009 pandemic (pH1N1), SARS-CoV-2 infection is likely to lead to more severe disease, with multi-organ effects, including cardiovascular disease. SARS-CoV-2 has been associated with acute and long-term cardiovascular disease, but the molecular changes that govern this remain unknown.

Nanobiomaterials to modulate natural killer cell responses for effective cancer immunotherapy.

Natural killer (NK) cells have emerged as a major target for cancer immunotherapies, particularly as cellular therapy modalities because they have relatively less toxicity than T lymphocytes. However, NK cell-based therapy suffers from many challenges, including problems with its activation, resistance to genetic engineering, and large-scale expansion needed for therapeutic purposes. Recently, nanobiomaterials have emerged as a promising solution to control the challenges associated with NK cells.

TGFβ and CIS Inhibition Overcomes NK-cell Suppression to Restore Antitumor Immunity.

Antibodies targeting "immune checkpoints" have revolutionized cancer therapy by reactivating tumor-resident cytotoxic lymphocytes, primarily CD8+ T cells. Interest in targeting analogous pathways in other cytotoxic lymphocytes is growing. Natural killer (NK) cells are key to cancer immunosurveillance by eradicating metastases and driving solid tumor inflammation.