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Mala Maini describes a 1996 paper by Frank Chisari and colleagues that showed CD8⁺ T cells can exert potent antiviral efficacy against hepatitis B virus without lysing infected cells, through the production of antiviral cytokines.

Human challenge studies with SARS-CoV-2 have shown changes in the innate and adaptive immune response. Here the authors are examining potential correlates of infection in virus challenged recipients by assessing baseline immune parameters and how this predicts virus control.

Shared metabolic pathways could allow simultaneous manipulation of T cells, viruses and tumours. Here the authors show targeting cholesterol esterification restrains hepatitis B in vitro, whilst bolstering exhausted antigen-specific T cell responses from human liver and hepatocellular carcinoma.

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

Bacterial products in the gut–liver axis and tissue stromal factors can tune liver immunity by driving myeloid instruction of CD8⁺ T cells with immunomodulatory ability.

Evidence from animal models suggest a vital role for mucosal vaccination in inducing protection from coronavirus infection. Here the authors examine the B and T cell responses at the lower airways, and contrast humoral and cellular immunity of people after infection and vaccination.

Many cancer immune therapy approaches depend on an HLA-restricted neoantigen-specific T cell response. AUs show here that Zoledronic acid can expand, and induce tumour recognition by, a population of tissue resident memory gamma-delta T cells associated with an efficient anti-tumour immune response in hepatocellular carcinoma.

Seronegative healthcare workers with an innate signature of infection preferentially expand pre-existing T cells targeting the conserved replication transcription complex of SARS-CoV-2 in abortive infection.

Pallett et al. report that myeloid derived suppressor cells expand, home to the liver, and inhibit T cell-mediated liver damage in chronic hepatitis B virus infection.

A liver-intrinsic mechanism is presented that suppresses effective anti-hepatitis virus B responses in mice and humans by rendering virus-specific CD8 T cells refractory to activation causing loss of effector functions.

The burden of HBV infection remains high and new strategies to improve HBV vaccination and therapy are needed. Key research in 2016 highlights the efficacy of current approaches and proposes new concepts for some of the immunological defects that need to be overcome for HBV functional cure.

Authors utilise a cohort of healthcare workers, infected during the first wave of the SARS-CoV-2 pandemic, to assess symptom persistence and humoral and cellular immunity.

Barreby et al. identify a distinct subpopulation of human resident liver myeloid cells that expresses factors that act in a protective fashion against oxidative stress associated with NAFLD.

Comprehensive mapping reveals that functional CD4⁺ and CD8⁺ T cells targeting multiple regions of SARS-CoV-2 are maintained in the resolution phase of both mild and severe COVID-19, and their magnitude correlates with the antibody response.

Akbar and colleagues show that sestrins induce the reprogramming of non-proliferative, senescent-like CD27^–CD28^–CD8⁺ T cells to acquire an innate-like killing activity modulated by the NK receptor NKG2D and the adaptor molecule DAP12.

The tolerogenic properties of the liver make it an attractive site for infection by pathogens. This Review describes how most pathogens are effectively controlled by immune responses in the liver, and how some pathogens, such as hepatitis viruses and malaria-causing parasites, can establish chronic infections in the liver.

Currently, there is no cure for hepatitis B virus (HBV) infection, which can lead to chronic liver disease and liver cancer, and only a few biomarkers are available. This Roadmap provides an overview of HBV serum biomarkers and their challenges.

Multiple therapeutic approaches are being developed to achieve sustained, off-treatment suppression of HBV. In this Review, the authors examine T cell and B cell responses to HBV and the potential for immunotherapies to restore or release endogenous adaptive immunity by direct or indirect approaches.

In this Review, the authors consider various paths to functional cure of chronic hepatitis B (CHB) and the need to individualize therapy of this heterogeneous infection until a therapeutic avenue for all patients with CHB is available.

Immunotherapy is revolutionizing the treatment of many cancers and hepatocellular carcinoma (HCC) is no exception. This Review describes the heterogeneous immune microenvironments of HCC as well as their links with the various aetiologies underlying this malignancy and with response or resistance to immunotherapies. In addition, the authors provide an overview of the current landscape of clinical trials evaluating immunotherapies across all stages of HCC.