The failure of T cells to eradicate tumour cells in the tumour microenvironment is mainly due to the dysfunction of T cells. Senescent T cells, with defects in proliferation and effector functions, accumulate in ageing, chronic viral infections, and autoimmune disorders where antigen stimulation persists. Increasing evidence suggests that inducing T cell senescence is a key strategy used by malignant tumours to evade immune surveillance. In this review, we summarize the general features, functional regulation, and signalling network of senescent T cells in tumour development and highlight their potential as prognostic biomarkers in multiple cancer treatments, including chemotherapy, radiotherapy, and immunotherapy. Moreover, we discuss possible therapeutic strategies for preventing or rejuvenating senescence in tumour-specific T cells. Understanding these critical issues may provide novel strategies to enhance cancer immunotherapy.

Pembrolizumab, an anti‐programmed cell death protein 1 (PD‐1) antibody, has been shown to improve survival in patients with non‐small cell lung cancer (NSCLC) with high expression of programmed death‐ligand 1 (PD‐L1). Corticosteroids are the mainstay for most high‐grade immune‐related adverse events (irAEs) such as pembrolizumab‐induced hepatitis. However, the dose and duration of corticosteroid therapy are not well defined. The objective of this case report was to describe a new treatment pattern for severe immune checkpoint inhibitor‐associated hepatitis. Here, we report the case of a patient with metastatic lung adenocarcinoma who developed grade 3 immunotherapy‐induced hepatitis after the first cycle of pembrolizumab. Alanine aminotransferase (ALT) levels peaked at 233 U/L. Hepatitis was alleviated after the administration of methylprednisolone. Therefore, we retreated the patient with pembrolizumab. However, aminotransferase levels increased again after the initiation of low‐dose methylprednisolone or the reuse of pembrolizumab. Finally, hepatitis was controlled with low‐dose methylprednisolone plus bicyclol, a Chinese hepatoprotective agent. Although the patient had been on low‐dose methylprednisolone therapy for about six months, he showed a prompt response. During this period, we also found a dramatic decrease in the neutrophil‐lymphocyte ratio (NLR), senescent T cells (CD8+CD28−CD57+), and myeloid‐derived suppressor cells (MDSCs) in the peripheral blood of the patient. To our knowledge, this is the first case report of successful management of grade 3 pembrolizumab‐induced hepatitis with a combination of low‐dose corticosteroids and bicyclol. The durable clinical response and changes in blood biomarkers indicate that low doses of corticosteroids do not compromise the efficacy of immune checkpoint inhibitors (ICIs). Therefore, this case may provide a new treatment pattern for severe immunotherapy‐induced hepatitis.

Background: Aging is a critical risk factor for unfavorable clinical outcomes among COVID-19 patients and may affect vaccine efficacy. However, whether the senescence of T cells impact the progression to severe COVID-19 in the elderly individuals remains unclear. Methods: By using flow cytometry, we analyzed the frequency of senescent T cells (Tsens) in the peripheral blood from 100 elderly patients hospitalized for COVID-19 and compared the difference between mild/moderate and severe/critical illness. We also assessed correlations between the percentage of Tsens and the quantity and quality of spike-specific antibodies by ELISA, neutralizing antibody test kit and Elispot assay respectively, cytokine production profile of COVID-19 reactive T cells as well as plasma soluble factors by cytometric bead array (CBA). Results: We found a significant elevated level of CD4+Tsens in severe/critical disease compared to mild/moderate illness and patients with a higher level of CD4+Tsens (>19.78%) showed a decreased survival rate as compared to those with a lower level (<19.78%), especially in the breakthrough infection. The percentage of CD4+Tsens was negatively correlated with spike-specific antibody titers, neutralization ability and COVID-19 reactive IL-2+CD4+T cells. Additionally, IL-2 producing T cells and plasma levels of IL-2 were positively correlated with antibody levels. Conclusion: Our data illustrated that the percentage of CD4+Tsens in the peripheral blood could act as an efficient biomarker for the capacity of spike-specific antibody production and the prognosis of severe COVID-19, especially in the breakthrough infection. Therefore, restoration of the immune response of CD4+Tsens is one of the key factors to prevent severe illness and improve vaccine efficacy in older adults.

Matrix metalloproteinase 9 (MMP9), a zinc ion-dependent endopeptidase, is one of the most complex matrix metalloproteinases in the gelatinase family. During tissue remodeling, MMP9 leads to gelatin and collagen degradation, which in turn promotes tumor invasion and metastasis. However, comprehensive pan-cancer analysis has not been performed for MMP9. In addition, the diagnostic and prognostic value of MMP9 as a cancer biomarker remain poorly understood, as well as the utility of MMP9 expression as a predictor of immunological responses. Based on a comprehensive analysis of bioinformatics information, we investigated MMP9 expression in different cancers, correlations between MMP9 expression and cancer prognosis and gene mutations, and relationships between MMP9 expression and immune cell infiltration. Our results indicated that MMP9 was highly expressed in most malignant cancers. MMP9 expression was significantly positively or negatively associated with the clinical prognoses of patients with different kinds of cancer. Furthermore, MMP9 expression significantly correlated with infiltrating cells and the expression levels of immune checkpoint genes. This pan-cancer analysis provides comprehensive information on the potential value of MMP9 as a theranostic biomarker.