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Regulation of Leukocyte-Endothelial Cell Interactions in Tumor Immunity

  • Chapter
The Biology of Tumors

Part of the book series: Pezcoller Foundation Symposia ((PFSO,volume 9))

Abstract

Successful immunotherapy ultimately depends on the ability of immune effector cells to infiltrate tumor tissues. A major site of extravasation of immune effector cells out of the blood and into tissues occurs across specialized post-capillary high endothelial venules (HEV).1 Lymphocyte emigration into tissues involves a complex multistep adhesion cascade.2,3 The L-selectin leukocyte adhesion molecule is responsible for mediating the initial attachment and slow rolling of lymphocytes along the luminal surface of HEV under hemodynamic shear conditions, a crucial first step in the extravasation of immune effector cells into lymph nodes and Peyer’s patches as well as at extralymphoid sites. Firm adhesion of lymphocytes to HEV and transendothelial migration are dependent on the interaction of the leukocyte integrin, leukocyte function associated antigen-1 (LFA-1), with intercellular adhesion molecule-1 (ICAM-1) and ICAM-2 on endothelial cells. The α4β1 and α4β7 integrins have also been implicated in recruitment of lymphocytes to tissues through binding to their cognate receptors on endothelium including vascular cell adhesion molecule-1 (VCAM-1) and mucosal addressin cell adhesion molecule-1 (MAdCAM-1). Blockade of these leukocyte-endothelial cell adhesive interactions severely compromises anti-tumor immunity.4–7 The immune effector cells that are recruited to tissues via L-selectin-, LFA-1-, α4β1- and/or α4β7-dependent mechanisms include: naive and memory CD4 and CD8 T cells, monocytes, neutrophils, and CD56bright/CD56dim natural killer (NK) cell subsets.2,3,8

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Authors and Affiliations

  1. Department of Immunology, Roswell Park Cancer Institute, Buffalo, New York, 14263, USA

    Sharon S. Evans, Margaret Frey, David M. Schleider, Robert A. Bruce, Wan-chao Wang, Elizabeth A. Repasky & Michelle M. Appenheimer

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  1. Roswell Park Cancer Institute, Buffalo, New York, USA

    Enrico Mihich

  2. Kimmel Cancer Institute, Philadelphia, Pennsylvania, USA

    Carlo Croce

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Evans, S.S. et al. (1998). Regulation of Leukocyte-Endothelial Cell Interactions in Tumor Immunity. In: Mihich, E., Croce, C. (eds) The Biology of Tumors. Pezcoller Foundation Symposia, vol 9. Springer, Boston, MA. https://doi.org/10.1007/978-1-4899-1352-4_21

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