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A comparison of the repertoire of SARS-CoV-2-specific epitopes targeted by T cells induced by vaccination or natural infection reveals that T cells predominantly target non-spike epitopes in convalescent individuals, while there is a broader spike-specific CD8⁺ T-cell response in vaccinees. Despite differences in T-cell response, the targeted T-cell epitopes were conserved between the wild-type and Omicron variants in both groups.

Thimme and colleagues identify a molecular signature of T cell exhaustion resembling a ‘chronic scar’ that is imprinted in hepatitis C virus–specific CD8⁺ T cells and cannot simply be reversed by viral clearance.

Hepatitis C virus (HCV) variability and its phenotypic consequences aren’t well studied in relation to viral replication fitness and disease severity. Here, the authors identify a replication-enhancing domain in non-structural protein 5A, linking high replication fitness to severe disease outcomes, with implications for understanding HCV pathogenesis in immunocompromised patients.

Heim et al. investigate the role of CD8⁺ T cells specific to HBV polymerase in the context of chronic HBV infection. They identify a unique subset of CD8⁺ T cells with an attenuated effector function. The attenuation is driven by TGFβ signaling, offering new insights into the immune landscape of chronic HBV infection and suggesting potential therapeutic avenues for modulating these cells to enhance viral control.

Vaccines induce beneficial immunity for COVID-19, but immune waning prompts boosting vaccination. Here, the authors show that a third, boosting dose of COVID-19 mRNA vaccine induces transient CD8 + T effector cell response while conserving the CD8 memory T cell pool, thereby permitting reactivation of spike-specific CD8 + T cells upon breakthrough infection or 4th vaccination.

Longitudinal analyses of SARS-CoV-2 mRNA vaccine-elicited epitope-specific CD8⁺ T cell responses shows that CD8⁺ T cells are rapidly induced after prime vaccination and stably maintained after boost vaccination.

Human transplantation with allogeneic donor organs results in non-matching of MHC and differential presentation of T cell antigens. Here the authors show that in a lung transplanted SARS-CoV-2 infected patient T cell responses generated from the host may not be able to recognise infected cells within the graft and this may contribute to virus persistence.

Virus-specific CD8⁺T cells lose effector function over the course of chronic infection, a process called ‘exhaustion’, but the fate of these cells after treatment-induced antigen elimination is unknown. Here the authors show that exhausted cells persist in patients even after direct-acting antiviral therapy removes antigen exposure, and that these cells are responsive on re-exposure to antigen.

CD8⁺ T cells are functionally impaired during chronic HBV infection. Recent findings from preclinical models and studies of chronically infected humans have revealed surprising insights into the nature of the T cell dysfunction, which may open new avenues for therapeutic intervention.

Here the authors dissect the contribution of IL-21 signaling to immune checkpoint-responding CD8⁺ T cells from mouse models and patients being treated for advanced melanoma.

Functionally competent memory CD8⁺ T cells specific for different viral epitopes are induced by SARS-CoV-2 infection and can be detected in the absence of virus-specific antibodies.

Here, in a longitudinal case study, Weigang et al. demonstrate that evolution of SARS-CoV-2 within a persistently infected immunosuppressed patient can result in the emergence of novel variants with reduced sensitivity to antibody neutralization.

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.

Cancer is associated with higher risk of severe COVID-19 outcomes. Two studies prospectively analyze the immunological and clinical characteristics of a large cohort of patients with cancer following SARS-CoV-2 infection or vaccination, providing important clinical insights to improve the management of such vulnerable patients.

Understanding individual variations in the response to seasonal influenza vaccines has broad implications from basic immunology to public health. Here authors show that influenza hemagglutinin-specific T and B cell responses are determined by the pre-vaccination immune phenotype and vaccination history of recipients.

Our understanding of the immune response to SARS-CoV-2 infection is still incomplete. Here, the authors find that IL-33, produced during immune recall potentially by CD14⁺ monocytes, correlates with CD4⁺ T cell activation, anti-SARS-CoV-2 antibody titer, and disease severity in a cohort of convalescent individuals professionally exposed to the virus.

Combining the kinase inhibitor sorafenib with allogeneic stem cell transplantation boosts immune responses against a subtype of acute myelogenous leukemia, suggesting potential clinical benefit.

A genetic variant in the IFN-lambda 4 gene has been associated with poor hepatitis C virus prognosis but it is not clear how this functions. Here the authors show that IFN-lambda 4 promotes ER stress and inhibits presentation of HCV epitopes to CD8⁺ T cells.

Liver resident CD8 T cells have an essential role in immunopathology in a mouse model of nonalcoholic steatohepatitis, by becoming auto-aggressive following sequential transcriptional and metabolic activation steps .

The function of memory CD8⁺ T cells is often believed to be directly correlated with their localization in tissues. Here the authors show that CD8⁺T cells with different proliferative and cytotoxic properties can be distinguished based on their expression of CX3CR1, independently of their tissue localization.

To replicate in Huh7 hepatoma cells, HCV must acquire mutations that prevent PI4KA over-activation. PI4KA-specific inhibitors promote replication of unadapted viral isolates and allow replication of patient-derived virus in cell culture.

Mutations in the costimulatory molecule CTLA-4 in six families are associated with immune dysregulation.

TOX is a critical factor for the normal progression of T cell dysfunction and the maintenance of exhausted T cells during chronic infections.

Peng et al. find that immunodominant cytotoxic T lymphocytes (CTLs) specific for NP_105–113-B*07:02 are associated with reduced COVID-19 severity. Mechanistically, NP_105–113-B*07:02-specific CTLs show potent antiviral functionality and may represent rational T cell vaccine targets.

A study of hospitalized patients infected with SARS-CoV-2 and who have liquid or solid cancer suggests that hematologic malignancy is an independent risk factor for mortality and that CD8⁺ T cells might limit infection in this setting irrespective of humoral immunity.

Zehn and colleagues review the cellular fates and precursor trajectories that allow antigen-specific CD8⁺ T cells to persist in the face of chronic infection and cancer.

Sagar and colleagues provide a comprehensive single-cell multimodal landscape of γδ T cells in various mouse tissues, unveiling site-specific adaptations and highlighting key tissue residency features of γδ T cells.

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide. Treatment options for patients with advanced HCC are limited because of the lack of effective chemotherapeutic agents. This Review discusses the mechanisms of targeted therapies and describes clinical studies that have investigated the safety and efficacy of these therapies in patients with HCC. Perspectives for future developments are also provided.