Varied functions of immune checkpoints during cancer metastasis
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REVIEW
Varied functions of immune checkpoints during cancer metastasis Ali Safarzadeh1,2 · Mohsen Alizadeh1 · Fatemeh Beyranvand2 · Reza Falavand Jozaaee2 · Khalil Hajiasgharzadeh1 · Amir Baghbanzadeh1 · Afshin Derakhshani1,3 · Antonella Argentiero3 · Behzad Baradaran1 · Nicola Silvestris3,4 Received: 16 July 2020 / Accepted: 31 August 2020 © The Author(s) 2020
Abstract Immune checkpoints comprise diverse receptors and ligands including costimulatory and inhibitory molecules, which play monumental roles in regulating the immune system. Immune checkpoints retain key potentials in maintaining the immune system homeostasis and hindering the malignancy development and autoimmunity. The expression of inhibitory immune checkpoints delineates an increase in a plethora of metastatic tumors and the inhibition of these immune checkpoints can be followed by promising results. On the other hand, the stimulation of costimulatory immune checkpoints can restrain the metastasis originating from diverse tumors. From the review above, key findings emerged regarding potential functions of inhibitory and costimulatory immune checkpoints targeting the metastatic cascade and point towards novel potential Achilles’ heels of cancer that might be exploited therapeutically in the future. Keywords Immune checkpoints · Metastasis · Tumor · Immune system
Background Cancer is one of the most meaningful threatening diseases for human health and despite the endless efforts that took place during the lasts decades, the number of cancer victims reaches millions [1]. One of the most important causes of cancer mortality is metastasis, which is defined as the movement of cancerous cells from their primary sites toward other organs [2]. All the tumor cells would not metastasize because the intrinsic properties of tumor cells and the tumor microenvironment factors should move toward promoting the tumor metastasis [3]. The tumor microenvironment is comprised of a myriad of interactions between immune and * Behzad Baradaran [email protected] * Nicola Silvestris [email protected] 1
Immunology Research Center, Tabriz University of Medical Sciences, Daneshghah Ave, 5166614766 Tabriz, Iran
2
Student Research Committee, Lorestan University of Medical Sciences, Khorramabad, Iran
3
IRCCS IstitutoTumori “Giovanni Paolo II” of Bari, Bari, Italy
4
Department of Biomedical Sciences and Human Oncology, University of Bari “Aldo Moro”, 70124 Bari, Italy
tumor cells, which eventually, promote the immune system’s responses against the tumor cells through the regulation of inhibitory and costimulatory responses [4]. Immune checkpoints play substantial roles in self-tolerance as immunity regulators, which hinder the immune system’s attack against healthy cells and lower the risk of autoimmunity developing [5, 6]. T cell responses that play significant roles in the detection and eliminating of tumor cells are initiated through the detection of antigens by T cell receptors (TCRs) and are regulated through the making balance between i
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