Immunology

The role of T cells in the resolution or exacerbation of COVID-19, as well as their potential to provide long-term protection from reinfection with SARS-CoV-2, remains debated. Nevertheless, recent studies have highlighted various aspects of T cell responses to SARS-CoV-2 infection that are starting to enable some general concepts to emerge. In this Progress article, Zeyu Chen and E. John Wherry summarize early reports of the T cell responses observed in patients with COVID-19, emphasizing how different immune response characteristics in different patients may reflect a spectrum of disease phenotypes.

Metastatic disease is responsible for approximately 90% of cancer deaths. For successful dissemination and metastasis, cancer cells must evade detection and destruction by the immune system. This process is enabled by factors secreted by the primary tumour that shape both the intratumoural microenvironment and the systemic immune landscape. Here, we review the evidence of aberrant immune cell crosstalk in metastasis formation and the role that primary tumours play in hijacking these interactions in order to enhance their metastatic potential. Moreover, we highlight the intriguing parallels between the inflammatory pathways underlying inflammatory disorders and cancer progression. Immune subversion by primary tumours plays a key role in metastatic spread. This Review explores how primary tumours interfere with the crosstalk between immune cells to promote a chronic inflammatory yet immunosuppressed state that enables immune evasion and the formation of metastases.

Natural killer (NK) cells belong to the innate immune system and contribute to protecting the host through killing of infected, foreign, stressed or transformed cells. Additionally, via cellular cross-talk, NK cells orchestrate antitumor immune responses. Hence, significant efforts have been undertaken to exploit the therapeutic properties of NK cells in cancer. Current strategies in preclinical and clinical development include adoptive transfer therapies, direct stimulation, recruitment of NK cells into the tumor microenvironment (TME), blockade of inhibitory receptors that limit NK cell functions, and therapeutic modulation of the TME to enhance antitumor NK cell function. In this Review, we introduce the NK cell–cancer cycle to highlight recent advances in NK cell biology and to discuss the progress and problems of NK cell–based cancer immunotherapies. In this Review, Smyth and colleagues provide an overview of recent advances in NK cell biology and discuss the progress and problems of NK cell–based cancer immunotherapies.

Click here to edit the content

The protein expression profile of ACE2, suggested as host receptor for SARS‐CoV‐2, is assessed in various human organs. Notably, limited ACE2 expression is observed in the respiratory system both o

Inborn errors of immunity are genetic disorders with broad clinical manifestations, ranging from increased susceptibility to infections to significant immune dysregulation, often leading to multiple autoimmune phenomena, lymphoproliferation, and malignancy. The treatment is challenging as it requires careful balancing of immunosuppression in subjects at increased risk of infections. Recently, the improved ability to define inborn errors of immunity pathophysiology at the molecular level has set the basis for the development of targeted therapeutic interventions. Such a “precision medicine” approach is mainly bases on the use of available small molecules and biologics to target a specific cell function. In this article, we summarize the clinical and laboratory features of various recently described inborn errors of immunity associated with immune dysregulation and hyperinflammation in which mechanism-based therapeutic approaches have been implemented.

Understanding the clinical presentation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and prognosis in children is a major issue. Children often present mild symptoms, and some severe forms require paediatric intensive care, with in some cases a fatal prognosis. Our aim was to identify the epidemiological characteristics, clinical presentation, and prognosis of children with coronavirus disease 2019 (Covid-19) hospitalized in Paris suburb hospitals. In this prospective, observational, multicentre study, we included children hospitalized in paediatric departments of Paris suburb hospitals from 23 March 2020 to 10 May 2020, during the national lockdown in France with confirmed SARS-CoV-2 infection (positive RNA test on a nasopharyngeal swab) or highly suspected infection (clinical, biological, and/or radiological data features suggestive for SARS-CoV-2 infection). A total of 192 children were included for confirmed (n = 157) or highly suspected (n = 35) SARS-CoV-2 infection. The median age was one year old (interquartile range 0.125–11) with a sex ratio 1.3:1. Fever was recorded in 147 (76.6%) children and considered poorly tolerated in 29 (15.1%). The symptoms ranged from rhinorrhoea (34.4%) and gastrointestinal (35.5%) to respiratory distress (25%). Only 10 (5.2%) children had anosmia and five (2.6%) had chest pain. An underlying condition was identified in almost 30% of the children in our study. Overall, 24 (12.5%) children were admitted to paediatric intensive care units, 12 required mechanical ventilation, and three died. For children in Paris suburbs, most cases of Covid-19 showed mild or moderate clinical expression. However, one-eighth of children were admitted to paediatric intensive care units and three died.

Plasmacytoid dendritic cells (pDCs) are a major source of type I interferon (IFN-I). What other functions pDCs exert in vivo during viral infections is controversial, and more studies are needed to understand their orchestration. In the present study, we characterize in depth and link pDC activation states in animals infected by mouse cytomegalovirus by combining Ifnb1 reporter mice with flow cytometry, single-cell RNA sequencing, confocal microscopy and a cognate CD4 T cell activation assay. We show that IFN-I production and T cell activation were performed by the same pDC, but these occurred sequentially in time and in different micro-anatomical locations. In addition, we show that pDC commitment to IFN-I production was marked early on by their downregulation of leukemia inhibitory factor receptor and was promoted by cell-intrinsic tumor necrosis factor signaling. We propose a new model for how individual pDCs are endowed to exert different functions in vivo during a viral infection, in a manner tightly orchestrated in time and space. Plasmacytoid dendritic cells (pDCs) are a major source of type I interferon (IFN-I). Dalod and colleagues show that IFN-I production and T cell activation were performed by the same pDC, but these occurred sequentially and in different micro-anatomical locations during virus infection.