Abstract
Immunotherapy is a new pillar of cancer therapy that provides novel opportunities to treat solid tumors. In this context, the development of new drugs targeting immune checkpoints is considered a promising approach in colorectal cancer (CRC) treatment because it can be induce specific and durable anti-cancer effects. Despite many advances in the immunotherapy of CRC, there are still limitations and obstacles to successful treatment. The immunosuppressive function of the tumor microenvironment (TME) is one of the causes of poor response to treatment in CRC patients. For this reason, checkpoint-blocking antibodies have shown promising outcomes in CRC patients by blocking inhibitory immune checkpoints and enhancing immune responses against tumors. This review summarizes recent advances in immune checkpoint inhibitors (ICIs), such as CTLA-4, PD-1, PD-L1, LAG-3, and TIM-3 in CRC, and it discusses various therapeutic strategies with ICIs, including the double blockade of ICIs, combination therapy of ICIs with other immunotherapies, and conventional treatments. This review also delineates a new hopeful path in the combination of anti-PD-1/anti-PD-L1 with other ICIs such as anti-CTLA-4, anti-LAG-3, and anti-TIM-3 for CRC treatment.
Highlights
Colorectal cancer (CRC) is one of the prevalent malignancies with a high mortality rate worldwide [1,2,3]
PD-L2 is another known ligand for programmed death 1 (PD-1) that is expressed in approximately 40% of colorectal cancer (CRC) patients
Due to the lack of striking clinical studies done on anti-lymphocyteactivation gene 3 (LAG-3) in CRC patients, further research and evaluations are required in this field
Summary
Colorectal cancer (CRC) is one of the prevalent malignancies with a high mortality rate worldwide [1,2,3]. The current therapeutic approach at the early stages of CRC is surgery, followed by radiotherapy and chemotherapy [5]. These common treatments may give rise to several challenges, such as their side effects, and are often associated with the development of drug resistance [5,6]. The immune system has a significant role in halting tumor cell development As such, immunotherapy, such as using monoclonal antibodies (mAbs) that target immune checkpoints, could significantly impact the treatment process of various malignancies [12]. Other potential therapeutic approaches, such as combining ICIs and radiotherapy or chemotherapy, are considered
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