Cancer immunotherapy with immune checkpoint inhibitors (ICIs): potential, mechanisms of resistance, and strategies for reinvigorating T cell responsiveness when resistance is acquired

Abstract

Cancer is still the leading cause of death globally. The approval of the therapeutic use of monoclonal antibodies against immune checkpoint molecules, notably those that target the proteins PD-1 and PD-L1, has changed the landscape of cancer treatment. In particular, first-line PD-1/PD-L1 inhibitor drugs are increasingly common for the treatment of metastatic cancer, significantly prolonging patient survival. Despite the benefits brought by immune checkpoint inhibitors (ICIs)-based therapy, the majority of patients had their diseases worsen following a promising initial response. To increase the effectiveness of ICIs and advance our understanding of the mechanisms causing cancer resistance, it is crucial to find new, effective, and tolerable combination treatments. In this article, we addressed the potential of ICIs for the treatment of solid tumors and offer some insight into the molecular pathways behind therapeutic resistance to ICIs. We also discuss cutting-edge therapeutic methods for reactivating T-cell responsiveness after resistance has been established.

Tissue‐resident memory T cells in immunotherapy and immune‐related adverse events by immune checkpoint inhibitor

“…ICIs immunotherapy is a type of cancer treatment that works by inhibiting immune checkpoints on immune cells, thereby boosting immune responses against cancer cells. 93 TRM cells have been found…”

Current state and challenges of emerging biomarkers for immunotherapy in hepatocellular carcinoma (Review)

“…In addition to the combination of immune drugs, new anti-tumor therapies such as photodynamic therapy and photothermal therapy can increase the immune response of tumor cells by changing the TME, and demonstrate synergistic effects (110). Comprehensive ranking based on the fundamental molecular and cellular pharmacological foundations and relevant mechanisms of action to hit multiple targets, as well as further investigation of the next-generation immunotherapies for patients with primary and acquired drug resistance, may improve the prediction of the optimal strategies (111,112). Currently, there are no data available on the combined prediction of immunotherapy efficacy by several indicators in liver cancer.…”

Expression of c-erb-B2 oncoprotein as a neoantigen strategy to repurpose anti-neu antibody therapy in a model of melanoma

“…[1][2][3] However, up to 40 to 50% of these patients still die from melanoma or develop resistance to currently available immune checkpoint inhibitors. 4,5 While there are other targeted agents available for melanomas with BRAF mutations, durability of their response is limited. 6 Adverse events from immunotherapy or targeted therapies also limit their use, and there are populations of patients in whom immune checkpoint blockade is contraindicated, such as those with organ transplants.…”