Reviews & Analysis

CD8⁺ tissue resident memory T cells (T_RM cells) are essential for defence against pathogens and malignancies. Prior work had indicated that these cells form within inflamed tissue, but there is emerging evidence that a pool of T_RM cell precursors exists within the circulation. This Review examines the processes and signals within the lymphoid compartment that determine lineage decisions towards the formation of T_RM cells.

Atherosclerosis involves a maladaptive inflammatory response. This Review summarizes the contributions of key innate and adaptive immune cell subsets and describes diverse mechanisms that regulate their activation. It also discusses the feasibility of developing immune-targeted interventions, such as tolerogenic vaccines.

This Progress article provides an update on the COVID-19 vaccine effort in the light of ongoing vaccine efficacy studies and real-world data on vaccine effectiveness, including the impact of virus variants of concern and challenges for global deployment.

This Progress article brings us up to date on the role of inflammasomes in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and COVID-19, describing how they may be activated during infection and contribute to the overexuberant inflammatory response in severe disease, and the efforts being taken to target them therapeutically.

Here, Ed Lavelle and Ross Ward discuss the unique aspects of mucosal immunity that must be considered when developing effective mucosal vaccines. The authors highlight the key immune cell populations that are targeted by mucosal vaccination strategies and explain how innovative adjuvant and delivery approaches should lead to new vaccines for infectious diseases and cancers.

In this Perspective, Murphy and Febbraio reflect on the advances that have been made in the past 20 years in developing therapies for cardiovascular and metabolic diseases that target the immune system. They also consider the potential of emerging immune-based therapies for these diseases.

Activation of nucleic acid-sensing Toll-like receptors is finely tuned to limit self-reactivity while maintaining recognition of foreign microorganisms. The authors describe recent progress made in defining the regulatory mechanisms that facilitate this delicate balance.

CD8⁺ T cells assume various dysfunctional states during tumorigenesis. Here, the authors describe mechanisms of T cell dysfunction in tumours, and what determines T cell responsiveness and resistance to immunotherapy.

Neutrophils are much more than just primary responders in infection. They influence tumour development and growth in many positive and negative ways. A growing appreciation of their diversity and plasticity is revealing their complex contributions to cancer depending on time, place and disease context.

Phase separation has emerged as a new biophysical principle for organizing biomolecules into large clusters with fluidic properties. Here, Su and colleagues summarize what we currently know about phase separation in immune cells and look to the future of this field in understanding the regulation of immune signalling.

This Review discusses the immunomodulatory effects of radiotherapy on both the tumour microenvironment and surrounding healthy tissue. The authors explain how radiotherapy can cause chronic inflammation and organ dysfunction in patients, and, in particular, they consider the impact of radiotherapy-induced immune effects in the lungs and intestine.

This Progress article summarizes our current understanding of the immune mechanisms of protection induced by the available COVID-19 vaccines. The authors compare vaccine-induced antibody responses following one or two doses of different vaccines and consider the relative importance of neutralizing antibodies for vaccine-mediated protection against SARS-CoV-2.

Vignali and colleagues discuss the pleiotropic roles of interferon-γ (IFNγ) in the tumour microenvironment; on the one hand, it acts as a ‘teammate’ to promote antitumour immune responses and, on the other hand, it acts as an ‘opponent’ promoting tumour growth and suppressing immune responses.

Emerging diseases that affect humans often arise due to the crossover of infectious agents from animal reservoirs. In this Perspective, George Warimwe and colleagues discuss the concept of ‘One Health vaccinology’, an approach that aims to use key lessons from human and veterinary immunology to develop more effective vaccination strategies for emerging infectious diseases.

The transcription factor TCF1 is essential for early T cell development, and recent advances have uncovered context-dependent functions in mature T cells. This review summarizes key findings on TCF1 across the field of T cell immunity and explores their translational potential.

This Review covers the role of natural killer cells in acute and chronic viral infections, with emphasis on human infections and insights from patients with primary immunodeficiencies affecting natural killer cells. It also describes the emerging data on how natural killer cells are involved in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.

In this Review, Maria Mittelbrunn and colleagues highlight the involvement of T cells in diseases associated with ageing. In particular, the authors discuss how T cells contribute to inflammageing and the potential of targeting these populations for therapy of age-related diseases.

In this Review, Iannacone and Guidotti discuss the immunobiology and pathogenesis of hepatitis B virus (HBV) infection, with a particular focus on the role of CD8⁺ T cells, and examine recent breakthroughs that challenge current dogmas.

This Review discusses our current understanding of the pathophysiological mechanisms of cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome associated with chimeric antigen receptor (CAR) T cell therapies, and how this might be used for the prevention or management of these toxicities.

This Review discusses evidence from clinical studies and animal models regarding the effects of the gut microbiota on modulating immune responses to vaccination as well as the immunological mechanisms that potentially mediate these effects.