Chemokines and T Cell Trafficking into Tumors: Strategies to Enhance Recruitment of T Cells into Tumors
Chemokines are small proteins used by the cells of the immune system in order to orchestrate their movement in the body during physiological and pathological conditions. Yet they are also expressed in tumors and their metastases. There, they mediate a var
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Chemokines and T Cell Trafficking into Tumors: Strategies to Enhance Recruitment of T Cells into Tumors Stefano Garetto, Claudia Sardi, Diego Morone, and Marinos Kallikourdis
Abstract Chemokines are small proteins used by the cells of the immune system in order to orchestrate their movement in the body during physiological and pathological conditions. Yet they are also expressed in tumors and their metastases. There, they mediate a variety of tumor-specific functions, including the recruitment of different immune cell populations to the tumor site. These cells may have a pro- or anti-tumoral function. Yet the cells mediating the latter are often prevented from infiltrating the tumor mass, due to functional or physical barriers. This is a major obstacle for successful tumor immunotherapy based on cytotoxic T cell administration. Genetic and other pre-clinical studies have provided insights into the mechanisms that regulate these barriers, such as the peri-tumoral fibrotic capsule. Recent novel strategies involving modification of the chemokine receptors expressed in the transferred cytotoxic T cells are providing a possible means of overcoming such obstacles. Integration of such strategies in immunotherapy protocols may hopefully pave the way to a more successful clinical application of T cell immunotherapy. Keywords Tumor • T cells • Adoptive Cell Therapy • Recruitment • Chemokines • Chemokine receptors
S. Garetto • C. Sardi Adaptive Immunity Laboratory, Humanitas Clinical and Research Center, Via Manzoni 56, Rozzano (Milano), Italy D. Morone Humanitas Clinical and Research Center, Via Manzoni 56, Rozzano (Milano), Italy M. Kallikourdis (*) Adaptive Immunity Laboratory, Humanitas Clinical and Research Center, Via Manzoni 56, Rozzano (Milano), Italy Humanitas University, Via Manzoni 113, Rozzano (Milano), Italy e-mail: [email protected] © Springer International Publishing Switzerland 2016 E. Donnadieu (ed.), Defects in T Cell Trafficking and Resistance to Cancer Immunotherapy, Resistance to Targeted Anti-Cancer Therapeutics 9, DOI 10.1007/978-3-319-42223-7_7
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Abbreviations ACT CAF CAR ECM FAP GPCR MDSC NK SHG TAM TCR TIL Treg VEGF
7.1
Adoptive cell therapy Cancer-associated fibroblasts Chimeric antigen receptor Extra cellular matrix Fibroblast Activation Protein-α G-protein-coupled receptors Myeloid-derived suppressor cells Natural Killer Second harmonic generation Tumor-associated macrophages T cell antigen receptor Tumor infiltrating Lymphocytes Regulatory T cells Vascular endothelial growth factor
Chemokines and Their Receptors
Chemokines (chemotactic cytokines) are small proteins divided into four subfamilies (CC, CXC, CX3C or XC), according to the position of conserved cysteine residues in their amino acid sequence [1, 2]. Chemokines are expressed and secreted by diverse cell types and each chemokine can bind to a cognate chemokine receptor, albeit with a certain degree of promiscuity. The chemokine receptors are seventransmembrane G-protein-coupled receptor
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