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    Locally injected lipid nanoparticles that deliver RNA to elicit danger signals and simultaneously contain RNA that encodes a membrane-anchored version of the cytokine IL-12 can induce immunogenic cell death in tumors. This multipronged platform induces anticancer immune responses to the injected lesion as well as to distant tumors and hence produces an abscopal effect.

    • Oliver Kepp
    •  & Guido Kroemer
  • News & Views |

    Deep learning can be used to predict genomic alterations on the basis of morphological features learned from digital histopathology. Two independent pan-cancer studies now show that automated learning from digital pathology slides and genomics can potentially delineate broader classes of molecular signatures and prognostic associations across cancer types.

    • Nicolas Coudray
    •  & Aristotelis Tsirigos
  • News & Views |

    The pre-metastatic niche is a complex microenvironment formed by the influence of tumor-derived factors on stromal and immune cells at distant sites of disseminated tumor-cell colonization. Signaling through the kinase p38α and regulation of the type I interferon receptor are now linked to formation of the pre-metastatic niche.

    • Sabina Kaczanowska
    •  & Rosandra N. Kaplan
  • News & Views |

    The approval of anti-TNF therapy for colitis over 20 years ago represented a paradigm shift for the treatment of this disease. Anti-TNF therapy is now shown to prevent colitis-associated colon cancer in mice by modifying the gut microbiota composition and transcriptional activity, including genes in Escherichia coli that control colibactin synthesis.

    • Giorgio Trinchieri
  • News & Views |

    KEAP1 is a tumor suppressor encoded by a gene commonly mutated in lung cancer. A systematic search for Keap1-mutant cancer vulnerabilities now reveals that Slc33a1 is a context-specific essential gene that represents a promising new anti-cancer target.

    • Luke A. Gilbert
  • News & Views |

    Natural killer (NK) cells serve a critical role in the control of metastasis. NK cells are now shown to preferentially control monoclonal metastases derived from single circulating tumor cells rather than polyclonal metastases derived from cell clusters. These findings provide further evidence that NK cells are linked to metastatic cell immunoediting.

    • Kyohei Nakamura
    •  & Mark J. Smyth
  • News & Views |

    Immune-checkpoint blockade holds great promise in cancer therapy; however, T cell–specific checkpoint inhibitors are not effective for all patients with cancer. The transcription factor c-Rel is now shown to regulate pro-inflammatory polarization of myeloid cells and modulate anti-tumor immune responses.

    • Hideyuki Takahashi
    •  & Judy Varner
  • News & Views |

    Studies of the tumor microenvironment have provided fundamental insights into cancer progression. A new study now delineates the dynamics of immune-cell alterations at the single-cell level and across stages of multiple myeloma, elucidating the microenvironmental changes involved in the precursor states of the disease.

    • Qiming Zhang
    •  & Zemin Zhang
  • News & Views |

    Small-cell lung cancer rapidly develops resistance to standard-of-care therapy. Two papers now establish xenograft models derived from patient-derived circulating tumor cells and show that initially homogeneous, chemoresponsive tumors rapidly recur as heterogeneous drug-refractory disease.

    • Anton Berns
  • News & Views |

    Despite recent advances in cancer treatment, metastasis and therapy resistance remain among the major causes of cancer-related deaths worldwide. A recent pan-cancer study provides a comprehensive molecular profile of advanced and post-therapy tumors, integrating whole-genome and transcriptomic analysis with clinical outcomes.

    • Esther Rheinbay
  • News & Views |

    Dysregulation of innate immune signaling in cancer can be pro-tumorigenic and can promote adaptive resistance to targeted therapies. Type I interferon signaling is now shown to promote survival following inhibition of the kinase EGFR, even in cells that are not ‘addicted’ to EGFR signaling.

    • Ryohei Yoshida
    •  & David A. Barbie
  • News & Views |

    Although many metabolic dependencies of cancer cells are well documented, altered cancer metabolism has not always been considered an active driver of tumorigenesis. Restrictive glutamine availability is now shown to promote colorectal cancer by lowering α-ketoglutarate levels and thereby promoting DNA hypermethylation, Wnt signaling and cellular de-differentiation.

    • Dana Krauß
    •  & Eyal Gottlieb
  • News & Views |

    To demonstrate the long-range effects of CD8+ T cell–secreted interferon-γ on bystander tumor cells, two studies now use mosaic models of antigen loss in tumors combined with intravital imaging. Factors that influence the length scale of diffusible signals could shape disease progression in cancer and autoimmunity.

    • Kenneth H. Hu
    •  & Matthew F. Krummel
  • News & Views |

    Tumor heterogeneity remains an obstacle to effective clinical management of breast cancer. Two new studies use high-dimensional imaging of single-cell protein expression in situ in clinical samples to link genomic alterations to multi-cellular features of the tumor microenvironment and reveal breast-cancer phenotypes associated with clinical outcome.

    • Leeat Keren
    •  & Michael Angelo
  • News & Views |

    Discerning and analyzing the mutational patterns that arise in the cancer genome can provide essential information on the process of tumorigenesis. An analytical framework and web-based tool now aim to aid in mutational signature assignment for improved tumor stratification.

    • Giovanni Ciriello
  • News & Views |

    Identifying indicators of response to immunotherapy is key for treatment decisions. Two studies now report that early changes in T cell repertoires and CD8+ memory effector cytotoxic T cells in peripheral blood correlate with response to immune-checkpoint inhibitors in metastatic melanoma and may serve as actionable biomarkers of immune activation.

    • Genevieve M. Boland
    •  & Keith T. Flaherty
  • News & Views |

    Drug repurposing is an attractive strategy for extending the arsenal of oncology therapies. Screening of a large collection of existing non-oncology compounds against a panel of cancer cell lines now identifies several drugs capable of selectively inhibiting the growth of cancer cells.

    • Roderick L. Beijersbergen
  • News & Views |

    Metastasis competence can be acquired early in tumorigenesis, although its underlying molecular intricacies remain unclear. A recent study provides key information about the function of L1CAM in conferring metastasis-initiation potential and chemoresistance in colorectal cancer by hijacking epithelial regenerative mechanisms.

    • Gloria Pascual
    •  & Salvador A. Benitah
  • News & Views |

    Immunotherapy resistance is associated with poor T cell infiltration into tumors. Tumor-cell-intrinsic oncogenic events that contribute to this defect include Wnt–β-catenin activation. PAK4 is now identified as an upstream modulator of this pathway, thus suggesting the potential of enhancing the efficacy of immunotherapy by targeting this druggable kinase.

    • Thomas F. Gajewski
    •  & Jessica Fessler
  • News & Views |

    Identifying cancer driver mutations is essential to understand disease biology and devise effective therapies, but remains a complex endeavor. A focused analytical approach is now presented that defines driver mutations affecting ubiquitin-mediated proteolysis through machine learning and mining of cancer multi-omics data.

    • Han Liang