PD‐1/PD‐L1‐dependent immune response in colorectal cancer

• Published in: Journal of cellular physiology Vol. 235; no. 7-8; pp. 5461 - 5475
• Main Authors: Payandeh, Zahra, Khalili, Saeed, Somi, Mohammad Hossein, Mard‐Soltani, Maysam, Baghbanzadeh, Amir, Hajiasgharzadeh, Khalil, Samadi, Nasser, Baradaran, Behzad
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01-07-2020
• Subjects: Apoptosis; B7-H1 Antigen - antagonists & inhibitors; B7-H1 Antigen - genetics; B7-H1 Antigen - immunology; Cancer; Cancer therapies; Cell death; Chemotherapy; Colorectal cancer; Colorectal carcinoma; Colorectal Neoplasms - genetics; Colorectal Neoplasms - immunology; Colorectal Neoplasms - therapy; Cytotoxicity; Gene Expression Regulation, Neoplastic - drug effects; Humans; Immune checkpoint; Immune Checkpoint Inhibitors - adverse effects; Immune Checkpoint Inhibitors - therapeutic use; immune checkpoint receptors; Immune response; Immune system; Immunotherapy; Immunotherapy - adverse effects; Localization; Lymphocytes; Lymphocytes T; Metastases; Microsatellite instability; Microsatellite Instability - drug effects; miRNA; Molecular modelling; Monoclonal antibodies; Patients; PD-1 protein; PD-L1 protein; Pembrolizumab; Programmed Cell Death 1 Receptor - antagonists & inhibitors; Programmed Cell Death 1 Receptor - genetics; Programmed Cell Death 1 Receptor - immunology; programmed cell death‐1; programmed cell death‐ligand 1; Targeted cancer therapy; Th1 Cells - drug effects; Th1 Cells - immunology; Tumor Microenvironment - drug effects; colorectal cancer; programmed cell death-ligand 1; immune checkpoint receptors; programmed cell death-1; immunotherapy
• ISSN: 0021-9541; 1097-4652
• DOI: 10.1002/jcp.29494

Colorectal cancer (CRC) is still considered as the third most frequent cancer in the world. Microsatellite instability (MSI), inflammation, and microRNAs have been demonstrated as the main contributing factors in CRC. Subtype 1 CRC is defined by NK cells infiltration, induction of Th1 lymphocyte and cytotoxic T cell responses as well as upregulation of immune checkpoint proteins including programmed cell death‐1 (PD‐1). Based on the diverse features of CRC, such as the stage and localization of the tumor, several treatment approaches are available. However, the efficiency of these treatments may be decreased due to the development of diverse resistance mechanisms. It has been proven that monoclonal antibodies (mAbs) can increase the effectiveness of CRC treatments. Nowadays, several mAbs including nivolumab and pembrolizumab have been approved for the treatment of CRC. Immune checkpoint receptors including PD‐1 can be inhibited by these antibodies. Combination therapy gives an opportunity for advanced treatment for CRC patients. In this review, an update has been provided on the molecular mechanisms involved in MSI colorectal cancer immune microenvironment by focusing on PD‐ligand 1 (PD‐L1) and treatment of patients with advanced immunotherapy, which were examined in the different clinical trial phases. Considering induced expression of PD‐L1 by conventional chemotherapeutics, we have summarized the role of PD‐L1 in CRC, the chemotherapy effects on the PD‐1/PD‐L1 axis and novel combined approaches to enhance immunotherapy of CRC by focusing on PD‐L1.
Schematic representation of different strategies to the modulation of the expression and function of the programmed cell death‐1 (PD‐1) in colorectal cancer (CRC). This protein is involved in multiple aspects of CRC development and PD‐1‐based therapies are promising therapeutic strategies for patients suffering from CRC.