New developments in the mechanism and application of immune checkpoint inhibitors in cancer therapy (Review)

Abstract

The use of immune checkpoint inhibitors (ICIs) has been demonstrated in the treatment of numerous types of cancer and ICIs have remained a key focus of cancer research. However, improvements in survival rates only occur in a subset of patients, due to the complexity of drug resistance. Therefore, further investigations are required to identify predictive biomarkers that distinguish responders and non-responders. Combined therapeutics involving ICIs and other modalities demonstrate potential in overcoming resistance to ICIs; however, further preclinical and clinical trials are required. Concurrently, prompt recognition and intervention of immune-related adverse events are crucial to optimize the use of ICIs in clinical treatment. The present study aimed to review the current literature surrounding the mechanisms and application of ICIs, with the aim of providing a theoretical basis for clinicians.

Rare, late onset of immune checkpoint inhibitor-induced type 1 diabetes mellitus in a patient with small-cell lung cancer treated with serplulimab: a case report and review of the literature

“…Although ICIs did not enter the market until 2011, they have been widely used in recent years, ranking second among the oncology products approved by the FDA [ 10 ]. ICIs do not directly kill tumor cells but rather counterbalance the tumor mechanism, reverse immune escape, activate immune response, and promote the killing of tumor cells by immune cells via remodeling T lymphocyte toxicity [ 11 ]. This makes the long-term survival of patients with advanced malignant tumors possible and provides new therapeutic indications in the early stage [ 12 ].…”

Preclinical and Clinical Observations Implying Combination Therapy to Enhance the Efficacy of the Her-2/neu B-Cell Peptide-Based Vaccine HER-Vaxx and to Prevent Immune Evasion

“…Therefore, evaluation of additional cases for the expression of Her-2/neu and PD-L1 is necessary, and planned, to further support the proposed combination immunotherapy by vaccination against both targets; (2) The upregulation of other ICs, such as T-cell Immunoglobulin and Mucin containing protein-3 (TIM-3), Lymphocyte activation gene-3 (LAG-3), and B and T Lymphocyte Attenuator (BTLA), was not evaluated in this study. The upregulation or co-expression of these ICs, expressed on intra-tumoral CD8 T-cells, results in T-cell exhaustion, reduced avidity and, consequently, tumor cells’ immune evasion [ 37 , 38 , 39 , 40 ]. The combination of IC inhibitors and targeted drugs has shown significant synergistic effects [ 41 , 42 , 43 ], and several clinical trials are ongoing to evaluate the combination of Her-2/neu-targeted therapy and ICIs in breast cancers [ 44 ].…”

Preclinical and Clinical Observations Implying Combination Therapy to Enhance the Efficacy of the Her-2/Neu B Cell Peptide-Based Vaccine Her-Vaxx and to Prevent Immune Evasion

“…Therefore, evaluation of additional cases for the expression of Her-2/neu and PD-L1 is necessary, and planned, to further support the proposed combination im-munotherapy by vaccination against both targets; (2) The upregulation of other ICs, such as T-cell Immunoglobulin and Mucin containing protein-3 (TIM-3), Lymphocyte activation gene-3 (LAG-3), and B and T Lymphocyte Attenuator (BTLA), was not evaluated in this study. The upregulation or co-expression of these ICs, expressed on intra-tumoral CD8 T-cells, results in T-cell exhaustion, reduced avidity and, consequently, tumor cells' immune evasion [37][38][39][40]. The combination of IC inhibitors and targeted drugs has shown significant synergistic effects [41][42][43], and several clinical trials are ongoing to evaluate the combination of Her-2/neu-targeted therapy and ICIs in breast cancers [44].…”