T Cell Dysfunction and Exhaustion in Cancer

Abstract

Tumor immunotherapy is a promising therapeutic strategy for patients with advanced cancers. T cells are key mediators of antitumor function that specifically recognize and react to tumor-expressing antigens and have proven critical for cancer immunotherapy. However, T cells are not as effective against cancer as expected. This is partly because T cells enter a dysfunctional or exhausted state, which is characterized by sustained expression of inhibitory receptors and a transcriptional state distinct from that of functional effector or memory T cells. T cell dysfunction induces the out of control of tumors. Recently, T cell dysfunction has been investigated in many experimental and clinical settings. The molecular definition of T cell dysfunction and the underlying causes of the T cell dysfunction has been advanced regardless of the fact that the pathways involved are not well elucidated, which proposing promising therapeutic opportunities in clinic. In this review, we will discuss the recent advances in the molecular mechanisms that affect TME and induce T cell dysfunction, and the development of promising immunotherapies to counteract the mechanisms of tumor-induced T cell dysfunction. Better understanding these underlying mechanisms may lead to new strategies to improve the clinical outcome of patients with cancer.

Nuclear Respiratory Factor 1 Associated with Prognosis and Immune Infiltration in Hepatocellular Carcinoma

“…Tumor immunotherapy is a promising and transformative therapeutic strategy for patients with advanced cancers [26,27]. Our data also demonstrated that NRF1 expression correlated with the in ltration status of B cells, CD4 + and CD8 + T cells, macrophages, neutrophils, and DCs.…”

Differential gene expression of tumor-infiltrating CD4 + T cells in advanced versus early stage colorectal cancer and identification of a gene signature of poor prognosis

“…The tumor microenvironment is highly heterogenous with the TILs constituting the vast majority of immune infiltrates. 33 The chronic exposure of cancer antigen to the memory T cells could alter their differentiation and activation, leading to exhaustion. 34 It has been reported that T-cell exhaustion is initiated in early stages after the onset of tumor in preclinical tumor models.…”

PD-1 upregulation enhances the immunosuppression of group 2 innate lymphoid cells by boosting IL-4 and IL-13 secretion in human non-small cell lung cancer

“…We found that CRTH2 and ST2 expression was more upregulated in PD-1 high ILC2s than in PD-1 low ILC2s. Since an inhibitory factor in later stages, similar to cytotoxic T cells (32). Indeed, a previous study demonstrated that PD-1 expression on ILC2s was upregulated after ILC2 activation by IL-33 in obese mice (40).…”