bims-nakice Biomed News
on Natural killer cells
Issue of 2026–09–06
seven papers selected by
Santosh Phuyal, Oslo Universitetssykehus
  1. Surfaceome CRISPR activation screening uncovers ligands regulating tumor sensitivity to NK cell killing.
  2. Towards reliable tracking of natural killer cells using commercial iron oxide nanoparticles and magnetic particle imaging.
  3. Mitochondrial Complex I at the Crossroads of NK cell Dysfunction in Glioblastoma.
  4. Ratiometric transcriptional activation by protein degradation.
  5. RAC2 orchestrates immune cell actin remodeling and migration.
  6. Horizontal mitochondrial transfer: an emerging field in cell biology.
  7. Precise DNA base editing using ContactSeek.
  1. Nat Commun. 2026 Aug 06. pii: 9442. [Epub ahead of print]17(1):
    Surfaceome CRISPR activation screening uncovers ligands regulating tumor sensitivity to NK cell killing.
    Ravi K Dinesh, Xiaotong Wang, Imran A Mohammad, Pari Gunasekaran, Kostas Stiklioraitis, Jeremy R Villafuerte, Anirudh Rao, Rogelio A Hernandez-Lopez, John B Sunwoo, Le Cong.
      Natural killer (NK) cell-based immunotherapies are promising for cancer treatment due to their ability to eliminate cancer cells independently of antigen presentation and "off-the-shelf" utility. However, molecular determinants governing tumor susceptibility to NK cytotoxicity remain incompletely understood. Here we employ CRISPR activation (CRISPRa) screening to identify cancer cell surface regulators of NK killing. Using a surfaceome-focused library, we screen human and murine cancer cell lines co-cultured with NK cells, identifying known and novel ligands modulating NK cytotoxicity. Screens reveal established factors including CD43 and previously uncharacterized regulators CD44, PDPN, and Siglec-1/CD169. Validation with orthogonal approaches confirm that disruption of these factors alters NK killing susceptibility in vitro and in humanized mouse models. Mechanistically, we find that CD43-mediated NK resistance operates independently of its proposed interaction with Siglec-7, and that targeting CD43 on NK cells or CAR T cells substantially enhances cytotoxic activity against leukemia. These results establish gain-of-function surfaceome screening as a powerful tool for identifying therapeutic targets for NK cell-based immunotherapy.
    DOI:  https://doi.org/10.1038/s41467-026-76374-x
  2. Biomater Sci. 2026 Aug 31.
    Towards reliable tracking of natural killer cells using commercial iron oxide nanoparticles and magnetic particle imaging.
    Suzanne Lightsey, Victoria Consalvo, Sk Rajab Ali, Daniela Paola Valdés, Jeremiah L Oyer, Grace Gloger, Alicja Joanna Copik, Carlos Rinaldi-Ramos, Blanka Sharma.
      Non-invasive tracking of natural killer (NK) cells remains a major challenge in cancer immunotherapy, limiting our understanding of their in vivo migration and persistence. Magnetic particle imaging (MPI) offers a quantitative, real-time method for visualizing labeled cells, yet optimal labeling protocols for NK cells have not been established. Here, we evaluate commercially available iron oxide nanoparticles (IONPs) for MPI labeling of both NK92MI cells and primary human NK cells. Labeled cells retained viability and cytotoxicity, including activity against three-dimensional tumor spheroids, and were detectable by MPI. To further examine imaging performance in a biologically relevant context, we employed mouse phantoms that recapitulate organ-specific signal distributions, enabling evaluation of quantification and liver spillover effects. We identify key tradeoffs between particle colloidal stability and per-cell iron content; specfically, VivoTrax and VivoTrax Plus provided higher MPI signal but required post-labeling purification, reducing cell recovery, whereas Synomag-D and Perimag were more stable and preserved cell yield despite lower signal intensity per cell. These results provide a framework for selecting nanoparticles that balance detection sensitivity, cell viability, and workflow practicality, advancing non-invasive NK cell tracking.
    DOI:  https://doi.org/10.1039/d6bm00655h
  3. Cancer Discov. 2026 Sep 01. 16(9): 1727-1729
    Mitochondrial Complex I at the Crossroads of NK cell Dysfunction in Glioblastoma.
    Silvia Tiberti, Katayoun Rezvani, May Daher.
      Zhou and colleagues identify mitochondrial complex I activity, mediated through NDUFA9, as a critical determinant of natural killer (NK) cell metabolic fitness and antitumor function in glioblastoma. Their study links impaired oxidative phosphorylation to glutamine dependence, epigenetic repression of effector programs, and loss of NK cell activity, highlighting mitochondrial fitness as an actionable axis for improving cellular immunotherapy in solid tumors. See related article by Zhou et al., p. 1924.
    DOI:  https://doi.org/10.1158/2159-8290.CD-26-1267
  4. Cell. 2026 Sep 01. pii: S0092-8674(26)00936-0. [Epub ahead of print]
    Ratiometric transcriptional activation by protein degradation.
    Melissa A Gray, Katelyn L Randal, Jennifer A Co, Michelle T Tang, Athena Z Xue, Sophia W Chen, Hlib Razumkov, Qusay Q Omran, David E Solow-Cordero, Jeonghye Yu, Stephanie A Robinson, Cara A Starnbach, Nathanael S Gray, Steven M Corsello, Steven M Banik.
      Cells can respond to alterations in the abundances of specific proteins through transcriptional outputs. Synthetic approaches inspired by native post-transcriptional circuits that convert protein abundance changes into programmable gene expression would be transformative. Here, we discover and describe design principles that effectively convert protein degradation into transcriptional outputs in live cells. We define ratiometric transcriptional activation, where control over the ratio between a transcription factor and a protein of interest fused to its inhibitor enables detection of abundance changes with high sensitivity at scale. We show that ratiometric transcriptional activation can be implemented in single cells using triply orthogonal circuits or in multicellular pools, operating independently of the mechanism of protein downregulation and enabling simultaneous detection of multiple protein downregulation events through outputs such as cell survival, fluorescent protein expression, or barcode sequencing. These circuits can be applied to oncogenic targets and enable discovery of new molecular glue degraders.
    Keywords:  CRISPR; PROTAC; amplification; anti-CRISPR; gene circuits; high-throughput; molecular glue; multiplexed circuits; proteostasis detection; synthetic biology; synthetic circuits; targeted protein degradation
    DOI:  https://doi.org/10.1016/j.cell.2026.08.009
  5. Front Immunol. 2026 ;17 1917716
    RAC2 orchestrates immune cell actin remodeling and migration.
    Kayleigh A Berthiaume Fox, Emily R Galvin, Geoffrey C Gurtner, Kellen Chen.
      In this review, we comprehensively summarize how RAC2+ innate immune cells contribute to a spectrum of immune dysregulation and disease states across multiple organ systems in humans. Our lab has recently identified RAC2's critical role in immune cell biology in the context of human and murine wound healing and fibrosis, induced by aberrant mechanical signaling. Thus, we sought to investigate the role of RAC2 in human immune cells. Here, we summarize the effects of gain-of-function (GOF), loss-of-function (LOF), and null RAC2 mutations on neutrophil phenotypes. As such, we propose a novel mechanism for RAC2-dependent biphasic neutrophil migration, critical for these cells in migrating to sites of injury across many disease states, including wound healing and fibrosis. Innate immune cells circulate and home to injury sites during the initial healing phases in all organs, therefore, understanding RAC2 regulation of neutrophil functions may reveal new avenues for systemic immunomodulatory therapies to treat immune dysregulation, and to better characterize mechanisms of wound healing and fibrosis.
    Keywords:  RAC2 GTPase; actin polymerization; chemotaxis; fibrosis; inborn errors of immunity (IEI); neutrophil functions; superoxide production; wound healing
    DOI:  https://doi.org/10.3389/fimmu.2026.1917716
  6. Trends Cell Biol. 2026 Sep 04. pii: S0962-8924(26)00168-6. [Epub ahead of print]
    Horizontal mitochondrial transfer: an emerging field in cell biology.
    Michael V Berridge, Zuzana Nahacka, Katerina Komrskova, Minghao Zheng, Jiri Neuzil.
      The field of horizontal mitochondrial transfer (HMT), also referred to as intercellular mitochondrial transfer, has recently gained momentum due to an increasing number of publications that go well beyond diseases such as cancer. From co-culture experiments to in vivo evidence in mouse cancer models, noncancerous diseases, and normal tissue and organ homeostasis and development, it is becoming increasingly clear that HMT is a fundamental physiological phenomenon broadly relevant to complex organisms. Recent methodological advances, epitomized by ultra-high-resolution microscopy and spatial and single-cell multiomics technologies, allow for research that strongly supports HMT as an emerging area of cell biology.
    DOI:  https://doi.org/10.1016/j.tcb.2026.08.012
  7. Nat Methods. 2026 Sep;23(9): 1679
    Precise DNA base editing using ContactSeek.
    Arunima Singh.
      
    DOI:  https://doi.org/10.1038/s41592-026-03230-7
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