Basic Rules of T Cell Migration
The positive correlation of lymphocyte infiltration into solid tumors with the patient survival, as well as recent successes of checkpoint inhibitors enhancing antitumor responses, have kindled a huge interest in cancer immunotherapy. In fact, adoptive ce
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Basic Rules of T Cell Migration Jens V. Stein, Federica Moalli, and Markus Ackerknecht
Abstract The positive correlation of lymphocyte infiltration into solid tumors with the patient survival, as well as recent successes of checkpoint inhibitors enhancing antitumor responses, have kindled a huge interest in cancer immunotherapy. In fact, adoptive cell therapy (ACT) of tumor-recognizing T cells has led to complete recession of tumors in a subset of melanoma patients. Yet, the molecular mechanisms that guide T cells to infiltrate tumor tissue for the detection and destruction of cancer cells are only incompletely understood. Here, we will give an overview on the basic rules of T cell migration, focusing on extra- and intracellular guidance cues gained primarily from intravital two photon imaging, and relate this with the efficient unfolding of adaptive immune responses. From this, we outline the challenges that T cells face entering and maneuvering inside non-lymphoid tissues including tumor sites. Keywords T cell trafficking • Integrins • Small GTPases • Intravital imaging • Extracellular matrix • Guanine exchange factors
J.V. Stein (*) • F. Moalli Theodor Kocher Institute, University of Bern, Bern 3012, Switzerland e-mail: [email protected]; [email protected] M. Ackerknecht Theodor Kocher Institute, University of Bern, Bern 3012, Switzerland Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, Basel 4058, Switzerland 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_1
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Abbreviations ACT APC ATX DC ECM FRC GALT GEF GPCR HEV LN LPA SLO TIL
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Adoptive cell therapy Antigen-presenting cell Autotaxin Dendritic cell Extracellular matrix Fibroblastic reticular cell Gut-associated lymphoid tissue Guanine exchange factor G-protein coupled receptor High endothelial venule Lymph node Lysophosphatidic acid Secondary lymphoid organ Tumor-infiltrating lymphocyte
Introduction
The adaptive immune system fulfills the critical task to protect against infectious microbes, including viruses and bacteria, while maintaining tolerance against self. The initiation of primary immune responses takes place in lymphoid tissues, such as skin-draining peripheral lymph nodes (LNs). There, the cellular arm of the adaptive immune system consisting of CD4+ and CD8+ T lymphocytes has evolved to quickly recognize pathogen-derived peptides displayed on major histocompatibility complexes (pMHC) by antigen-presenting cells (APCs) such as dendritic cells (DCs) and macrophages. The encounter of DCs or macrophages bearing cognate pMHC induces a “stop” signal for migrating T cells, i.e., these cells rapidly decrease their scanning behavior and engage in long-term interactions with DCs, which imprint a differentiation program leading to effector cell generation. Once activated, most CD8+ and
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