Progress in the Application of Immune Checkpoint Inhibitor-Based Immunotherapy for Targeting Different Types of Colorectal Cancer

Abstract

Colorectal cancer (CRC), a common malignant disease, has the second highest mortality rate among all cancer types. Due to the diversity and heterogeneity of CRC, few effective treatment strategies have been developed in recent years, except for surgical resection. As immunotherapy has become a revolutionary treatment after surgery, along with chemoradiotherapy and targeted therapy, numerous basic research studies and clinical trials have been conducted on CRC. Therefore, immune checkpoint inhibitor (ICI) therapy has become the main anti-CRC immunotherapy method used at present. With the rapid development of biotechnology and cell research, an increasing number of monotherapy or combination therapy strategies using ICIs for CRC have been designed in recent years. Methods to classify and review ICI strategies for different types of CRC to better guide treatment are continuously investigated. However, the identification of why the ICIs would be more effective in targeting particular subtypes of CRC such as high microsatellite instability (MSI-H) is more important because of the different immune backgrounds in patients. This review intends to classify different subtypes of CRC and summarizes the basic and clinical studies on ICIs for each subtype of CRC currently available. In addition, we also attempt to briefly discuss the progress in immunotherapy methods other than ICI therapy, such as chemoimmunotherapy strategy, chimeric antigen receptor-modified T (CAR-T) cells, or immunotherapy based on oncolytic viruses. Finally, we provide a perspective on the development of immunotherapy in the treatment of CRC and attempt to propose a new systematic classification of CRC based on immunological strategies, which may improve guidance for the selection of immunotherapy strategies for different subtypes of CRC in the future.

Comprehensive Analysis of a Cancer-Immunity Cycle–Based Signature for Predicting Prognosis and Immunotherapy Response in Patients With Colorectal Cancer

“…However, in treatment studies targeting mCRC, PD-L1 expression on tumor or immune cells has not been associated with ICI responses ( 30 – 32 ). Additionally, several other factors such as TMB ( 33 ), MSI ( 34 ), somatic copy-number alterations ( 35 ), T cell signaling ( 36 ), human leukocyte antigen (HLA) class I genotype ( 37 ), and TGFβ signaling ( 20 ) have been shown to correlate with the clinical outcome of ICIs therapy, based on molecular profiling of cancers treated with different immunotherapies. Unlike conventional cancer therapies, ICIs do not directly kill tumor cells; instead, they affect tumor cells through the patient’s immune system or the TME.…”

An Up-To-Date Investigation Into the Correlation Between Proton Pump Inhibitor Use and the Clinical Efficacy of Immune Checkpoint Inhibitors in Advanced Solid Cancers: A Systematic Review and Meta-Analysis

“…Generally, three representative ICIs have been commonly applied in clinical practice, including programmed cell death 1 (PD-1), programmed cell death ligand 1 (PD-L1), and cytotoxic drug T lymphocyte-associated antigen 4 (CTLA-4) inhibitors (1). However, despite encouraging results from clinical trials and the real world, a fairly large proportion of patients fail to benefit from ICI therapy due to various inherent and environmental factors, such as microsatellite instability, gut microbiota, and concomitant medications (2)(3)(4). Previously, our team has demonstrated that antibiotic administration shortly before or after ICI treatment is associated with poor clinical outcomes in patients with advanced solid cancers (5).…”

Current progress and future perspectives of neoadjuvant anti-PD-1/PD-L1 therapy for colorectal cancer

“…PD-1 and PD-L1 are a pair of important immune checkpoint (ICs) that work as the brake on the immune system and play a crucial role in the tumor immune escaping process (35). After the binding of PD-1 and PD-L1, tumor cells take advantage of the recognition of the T-cell receptor, further suppressing immunity and evading immune surveillance (36). In 2002, the evidence that the PD-1 pathway mediating tumor immunity was first reported in that the overexpression of PD-L1 will weaken the cytolytic activity of T cells and then significantly promote the occurrence and invasion of tumors (37).…”