Metabolic plasticity of T cell fate decision

The efficacy of adaptive immune responses in cancer treatment relies heavily on the state of the T cells.Upon antigen exposure,T cells undergo metabolic reprogramming,leading to the development of functional effectors or memory populations.However,within the tumor microenvironment(TME),metabolic stress impairs CD8+T cell anti-tumor immunity,resulting in exhausted differentiation.Recent studies suggested that targeting T cell metabolism could offer promising therapeutic opportunities to enhance T cell immunotherapy.In this review,we provide a comprehensive summary of the intrinsic and extrinsic factors necessary for metabolic reprogramming during the development of effector and memory T cells in response to acute and chronic inflammatory conditions.Furthermore,we delved into the different metabolic switches that occur during T cell exhaustion,exploring how prolonged metabolic stress within the TME triggers alterations in cellular metabolism and the epigenetic landscape that contribute to T cell exhaustion,ultimately leading to a persistently exhausted state.Understanding the intricate relationship between T cell metabolism and cancer immunotherapy can lead to the development of novel approaches to improve the efficacy of T cell-based treatments against cancer.

T cell cross-reactivity in autoimmune-like hepatitis triggered by COVID-19

Over 1000 cases of pediatric hepatitis of unknown etiology have been reported worldwide since the first case was reported in the UK.To date,the etiology of pediatric hepatitis remains unknown and controversial.Adenovirus was first suspected to be the cause as it was present in the blood samples of the majority of cases.Partial cases have also been tested positive for severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)[1].However,it is still unclear how these viruses contribute to pediatric hepatitis.In the case of a pediatric patient with SARS-CoV-2 infection,the liver biopsy showed acute submassive hepatocyte necrosis,accompanied by a significant increase in T cell infiltration[2].Furthermore,CD8+T cell dominant hepatitis induced by coronavirus disease 2019(COVID-19)vaccination has also been recently reported[3].Although it is known that T cell receptors(TCRs)can discriminate between self-and non-self-antigens,it is now well-accepted that TCRs exhibit cross-reactivity toward similar and even distinct antigen peptides[4].Thus,we hypothesized that following SARS-CoV-2 infection or vaccination,T cells carrying TCRs that recognize self-antigens undergo clonal expansion,which could eventually result in the onset of autoimmune-like hepatitis(Figure 1A).