Specifically activated memory T cell subsets from cancer patients recognize and reject xenotransplanted autologous tumors

The Journal of Clinical Investigation
Philipp BeckhoveViktor Umansky

Abstract

Bone marrow of breast cancer patients was found to contain CD8(+) T cells specific for peptides derived from breast cancer-associated proteins MUC1 and Her-2/neu. Most of these cells had a central or effector memory phenotype (CD45RA(-)CD62L(+) or CD45RA(-)CD62L(-), respectively). To test their in vivo function, we separated bone marrow-derived CD45RA(+) naive or CD45RA(-)CD45RO(+) memory T cells, stimulated them with autologous dendritic cells pulsed with tumor lysate, and transferred them into NOD/SCID mice bearing autologous breast tumors and normal skin transplants. CD45RA(-) memory but not CD45RA(+) naive T cells infiltrated autologous tumor but not skin tissues after the transfer. These tumor-infiltrating cells had a central or effector memory phenotype and produced perforin. Many of them expressed the P-selectin glycoprotein ligand 1 and were found around P-selectin(+) tumor endothelium. Tumor infiltration included cluster formation in tumor tissue by memory T cells with cotransferred dendritic cells. It was associated with the induction of tumor cell apoptosis and significant tumor reduction. We thus demonstrate selective homing of memory T cells to human tumors and suggest that tumor rejection is based on the recogniti...Continue Reading

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Citations

Jun 20, 2008·Cancer Immunology, Immunotherapy : CII·Malarvizhi DuraiJonathan P Schneck
Dec 4, 2009·Cancer Immunology, Immunotherapy : CII·Christoph DomschkePhilipp Beckhove
Oct 20, 2012·Cancer Metastasis Reviews·Stefan StefanovicChristoph Domschke
Dec 18, 2013·Cancer Metastasis Reviews·Stefan StefanovicChristoph Domschke
Aug 4, 2011·Cancer Microenvironment : Official Journal of the International Cancer Microenvironment Society·Israel VlodavskyMichael Elkin
Sep 23, 2009·Current Opinion in Oncology·Khashayarsha KhazaiePhilipp Beckhove
May 4, 2007·The Journal of Clinical Investigation·Carl H June
Nov 8, 2015·Cancer Letters·Nykia D WalkerPranela Rameshwar
Jul 31, 2007·Seminars in Cancer Biology·Jennifer M ReimanKeith L Knutson
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Apr 9, 2013·Pigment Cell & Melanoma Research·Viktor Umansky, Alexandra Sevko
Jan 26, 2010·Current Opinion in Cell Biology·Meredith A SteevesJohn L Cleveland
Dec 24, 2005·Pathology·Kristen J RadfordDerek N J Hart
Aug 23, 2005·Journal of Reproductive Immunology·Shin-Heng ChiouHo Hong-Nerng
Jan 7, 2015·The Journal of Clinical Investigation·Christoph ReissfelderPhilipp Beckhove
Jul 12, 2016·Pathophysiology : the Official Journal of the International Society for Pathophysiology·Mohammad W Khan, Viktor Umansky

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Methods Mentioned

BETA
biopsies
flow cytometry

Software Mentioned

FlowJo
Treestar
CELLQuest
KS ELISPOT

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