Immune checkpoint blockade in the treatment of malignant tumor: current statue and future strategies

Abstract

After being stagnant for decades, there has finally been a paradigm shift in the treatment of cancer with the emergence and application of immune checkpoint inhibitors (ICIs). The most extensively utilized ICIs are targeting the pathways involving programmed death-1 (PD-1) and cytotoxic T-lymphocyte associated protein 4 (CTLA-4). PD-1, as an crucial immune inhibitory molecule, by and large reasons the immune checkpoint response of T cells, making tumor cells get away from immune surveillance. Programmed cell death ligand-1 (PD-L1) is exceptionally expressed in most cancers cells and approves non-stop activation of the PD-1 pathway in the tumor microenvironment. PD-1/PD-L1 inhibitors can block the combination of PD-1 and PD-L1, inhibit hostile to regulatory signals, and restore the activity of T cells, thereby bettering immune response. The current researchers assume that the efficacy of these drugs is related to PD-L1 expression in tumor tissue, tumor mutation burden (TMB), and other emerging biomarkers. Although malignant tumors can benefit from the immunotherapy of PD-1/PD-L1 inhibitors, formulating a customized medication model and discovering biomarkers that can predict efficacy are the new trend in the new era of malignant tumor immunotherapy. This review summarizes the mechanism of action of PD-1/PD-L1 inhibitors, their clinical outcomes on various malignant tumors, their efficacy biomarkers, as well as predictive markers of irAEs.

Single-Cell Profiling Reveals Heterogeneity of Primary and Lymph Node Metastatic Tumors and Immune Cell Populations and Discovers Important Prognostic Significance of CCDC43 in Oral Squamous Cell Carcinoma

“…In the process of exploring the expression of tumor-immunity-related genes, it is found in the group with high expression of CCDC43 that the expression of antigen-presentation-related molecules, immune-related ligands, receptors, and co-suppressor molecules are generally downregulated ( Figure 5G ). We also found that the high expression of CCDC43 is closely related to the higher level of TMB ( Figure 5H ), while there is a significant negative correlation between TMB and the infiltration level of B cells, CD8+ T cells, and dendritic cells ( Figure 5I ), which suggests that high levels of TMB cannot be used as an effective predictor ( 36 ) in other cancers as previously reported. In addition, DNA damage repair (DDR) pathways were found to be significantly upregulated in the CCDC43 overexpression group ( Figure 5J ).…”

Toll-like receptor 9 agonists and combination therapies: strategies to modulate the tumour immune microenvironment for systemic anti-tumour immunity

“…Furthermore, there have been other issues concerning ICI therapies including adverse effects associated with autoimmunelike systemic symptoms (fatigue or fever) or organ-specific damage which may leads to rashes, colitis, pneumonia and adrenal or thyroid dysfunction [61,62]. Researchers found that ICIs only work in specific groups of people with certain types of cancers, such as melanoma, non-small-cell lung cancer (NSCLC), small cell lung cancer (SCLC), renal cell carcinoma (RCC), colorectal cancer (CRC), classical Hodgkin lymphoma (cHL), head and neck squamous cell carcinoma (HNSCC), hepatocellular carcinoma (HCC), primary mediastinal large B-cell lymphoma (PMLBCL), Merkel cell carcinoma (MCC), etc [63], while patients with other types of cancer showed a poor therapeutic effect. Therefore, scientists look for combination therapies combining ICI with other agents in the hope of achieving better results.…”

Development and validation of novel prognostic models for zinc finger proteins-related genes in soft tissue sarcoma

“…Additionally, unlike in other tumors, little progress improving survival of patients with advanced STS has been made despite the fact that radiotherapy, chemotherapy, immunotherapy and targeted therapy have been tried to treat patients with advanced STS [ 4 , 5 ]. According to previously published studies, a good deal of molecular biomarkers (such as PD1 and PDL1) play key roles in predicting prognosis and determining optimal treatment choices for various tumors [ 6 ]. Therefore, identifying novel molecular biomarkers and subsequent elucidation of the specific mechanisms through which these biomarkers affect STS may help us develop novel therapeutic strategies and improve prognosis.…”