Beclin-1 as a neutrophil-specific immune checkpoint

• Published in: The Journal of clinical investigation Vol. 129; no. 12; pp. 5079 - 5081
• Main Authors: Su, Yu-Lin, Kortylewski, Marcin
• Format: Journal Article
• Language: English
• Published: United States American Society for Clinical Investigation 01.12.2019
• Subjects: Angiogenesis; Animals; Antitumor activity; Autophagy; B cells; Beclin-1; Biomedical research; Cancer; Carcinogenesis; CD40 antigen; Clonal deletion; Cytokines; Development and progression; Functional plasticity; Genes; Genotype & phenotype; Humans; Immune checkpoint; Immunization; Immunostimulation; Immunotherapy; Inflammation; Interleukin 10; Interleukin 21; Kinases; Leukemia; Leukocytes (neutrophilic); Lungs; Lymphocytes B; Lymphoma; Medical research; Mice; Neutrophils; PD-L1 protein; Phagocytosis; Precursor Cells, B-Lymphoid; Trends; Tumors; Wound care; Wound healing; Wounds
• ISSN: 0021-9738; 1558-8238
• DOI: 10.1172/JCI132534

Neutrophils are early wound healing and inflammation regulators that, due to functional plasticity, can adopt either pro- or antitumor functions. Until recently, beclin-1 was a protein known mainly for its role as a critical regulator of autophagy. In this issue of the JCI, Tan et al. describe the effects of the beclin-1 conditional myeloid cell-specific deletion in mice, in which immunostimulation resulted in hypersensitive neutrophils. The chronic proinflammatory effect of these neutrophils triggered spontaneous B cell malignancies to develop. Such tumorigenic effects were mediated primarily by IL-21 and CD40 signaling, leading to the upregulation of tolerogenic molecules, such as IL-10 and PD-L1. The authors went on to examine samples derived from patient lymphoid malignancies and showed that beclin-1 expression in neutrophils positively correlated with pre-B cell leukemia/lymphoma. Overall, the study provides an elegant model for neutrophil-driven carcinogenesis and identifies potential targets for immunotherapy of B cell malignancies.