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  • Immunotherapeutic targeting of the surface glycoprotein CD19 has markedly improved outcomes in patients with relapsed and refractory B cell progenitor acute lymphoblastic leukemia. Genome-wide CRISPR–Cas9 screening identifies modulators of CD19 mRNA processing that affect the abundance of the surface protein in human B cell leukemia cells, with the potential to improve antigen-directed immunotherapy efficacy.

    Research Briefing
  • During T cell activation, tRNA-m1A ‘writers’ TRMT61A and TRMT6 are upregulated to modify a group of early tRNA species and promote efficient translation of certain pre-cell-cycling proteins, thus ensuring rapid T cell proliferation and a timely adaptive immune response.

    Research Briefing
  • Endosomal TLR7 and TLR9 recognize RNA and DNA ligands, respectively, and both signal via MyD88 yet appear to play opposing roles in autoimmunity. Shlomchik and colleagues examine this TLR ‘paradox’, reporting that TLR9 has two protective functions, including an as yet unidentified additional MyD88-independent signaling pathway that confers protection against autoimmunity.

    • Claire Leibler
    • Shinu John
    • Mark J. Shlomchik
  • Naive T cells are quiescent but undergo dynamic changes upon antigenic activation. Li and colleagues show that upregulation of tRNA methyltransferase complex TRMT61A–TRMT6 and N1-methyladenosine modification of tRNAs contribute to accelerated mRNA translation efficiency, in particular that of MYC protein, and are required for rapid T cell proliferation.

    • Yongbo Liu
    • Jing Zhou
    • Hua-Bing Li
  • The explosion of single-cell and systems approaches in immunology risks leaving the uninitiated behind. This guide to systems immunology is designed for immunologists who want an introduction to the area.

    • Lorenzo Bonaguro
    • Jonas Schulte-Schrepping
    • Joachim L. Schultze
    Review Article
  • Through access to healthy donors’ bronchoalveolar lavage (BAL) samples cryopreserved before the COVID-19 pandemic, we discovered CD4+ and CD8+ T cells able to cross-recognize SARS-CoV-2 among the airway tissue-resident memory pool. Pre-pandemic donors with detectable SARS-CoV-2-cross-reactive T cells in their airways also had stronger immunity to human seasonal coronaviruses.

    Research Briefing
  • Maini and colleagues used bronchoalveolar lavage (BAL) samples from the lower respiratory tract of healthy donors obtained before the COVID-19 pandemic to show airway-resident cross-reactive T cells are present in pre-pandemic BAL, and correlated with the strength of human coronavirus immunity

    • Mariana O. Diniz
    • Elena Mitsi
    • Mala K. Maini
    Letter Open Access
  • Intestinal group 3 innate lymphoid (ILC3) cells exhibit increased mobility in response to flagellin-mediated inflammation. This ‘patrolling’ behavior promotes IL-22 diffusion and prevents intestinal epithelial cell death. Enhanced ILC3 dynamics rely on environmental cues and suggest a prominent ILC3 tissue adaptation that reinforces intestinal barrier integrity.

    Research Briefing
  • The net effect of type I interferon (IFN-I) signaling on tumor control depends on various factors, including the potential engagement of adaptive anticancer immunity. New findings delineate a targetable epigenetic mechanism by which suboptimal IFN-I signaling promotes tumor progression in the context of cancer stem cell expansion and immunoevasion.

    • Lorenzo Galluzzi
    • Guido Kroemer
    News & Views
  • Type I interferons have been described to have protumor or antitumor functions depending on context. Here the authors show a protumor function for type I interferons in that they promote cancer stem cells by upregulating the chromatin remodeling factor KDM1B.

    • Martina Musella
    • Andrea Guarracino
    • Antonella Sistigu
    Article Open Access