Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden; Cell Therapy Institute, Nova Southeastern University, Ft Lauderdale, FL, USA. Electronic address:
Published: June 2017
AI Article Synopsis
Article Abstract
The contribution of natural killer (NK) cells to immunosurveillance of human cancer remains debatable. Here, we discuss advances in several areas of human NK cell research, many of which support the ability of NK cells to prevent cancer development and avoid relapse following adoptive immunotherapy. We describe the molecular basis for NK cell recognition of human tumor cells and provide evidence for NK cell-mediated killing of human primary tumor cells ex vivo. Subsequently, we highlight studies demonstrating the ability of NK cells to migrate to, and reside in, the human tumor microenvironment where selection of tumor escape variants from NK cells can occur. Indirect evidence for NK cell immunosurveillance against human malignancies is provided by the reduced incidence of cancer in individuals with high levels of NK cell cytotoxicity, and the significant clinical responses observed following infusion of human NK cells into cancer patients. Finally, we describe studies showing enhanced tumor progression, or increased cancer incidence, in patients with inherited and acquired defects in cellular cytotoxicity. All these observations have in common that they, either indirectly or directly, suggest a role for NK cells in mediating immunosurveillance against human cancer. This opens up for exciting possibilities with respect to further exploring NK cells in settings of adoptive immunotherapy in human cancer.
The use of pesticides has enabled the development of contemporary industrial agriculture and significantly increased crop yields. However, they are also considered a source of environmental pollution and a potential hazard to human health. Despite national agencies and the scientific community analyzing pesticide safety, immunotoxicity assays are often not required, poorly designed, or underestimated.
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The cerebrospinal fluid (CSF) border accommodates diverse immune cells that permit peripheral cell immunosurveillance. However, the intricate interactions between CSF immune cells and infiltrating cancer cells remain poorly understood. Here we use fate mapping, longitudinal time-lapse imaging and multiomics technologies to investigate the precise origin, cellular crosstalk and molecular landscape of macrophages that contribute to leptomeningeal metastasis (LM) progression.
Department of Hepatobiliary Surgery and Visceral Transplantation, Clinic and Polyclinic for Visceral, Transplant, Thoracic and Vascular Surgery, Leipzig University Medical Center, Leipzig, Germany.
The development of in vitro hepatocyte cell culture systems is crucial for investigating drug-induced liver injury (DILI). One prerequisite for monitoring DILI related immunologic reactions is the extension of primary human hepatocyte (PHH) cultures towards the inclusion of macrophages. Therefore, we developed and characterized an autologous co-culture system of PHH and primary human hepatic macrophages (hepM) (CoC1).
Immune responses to tumors, comprising adaptive T cells and innate NK cells, arise very early in tumorigeneses and prior to detection of palpable tumors or before tissue pathology is evident. Yet, how nascent tumors evoke dendritic cell maturation and the resulting cytokine responses that are necessary for these effector anti-tumor immune responses is unknown. We have previously shown that CD91 expression on dendritic cells is important for immune surveillance, specifically for generating T cell and NK cell responses to nascent tumors.
