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 recognition of tumor-associated antigens on tumor cells and dendritic cells by autologous specifically activated central and effector memory T cells.
Philipp Beckhove, Markus Feuerer, Mathias Dolenc, Florian Schuetz, Carmen Choi, Nora Sommerfeldt, Jochen Schwendemann, Katrin Ehlert, Peter Altevogt, Gunther Bastert, Volker Schirrmacher, Viktor Umansky
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Tumor-specific CD8+ T cells from the bone marrow resist exhaustion and exhibit increased persistence in tumor-bearing hosts as compared with tumor-infiltrating lymphocytes
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Journal for Immunotherapy of Cancer | 2025 |
Exploring the evolution of T cell function and diversity across different stages of non-small cell lung cancer
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American journal of cancer research | 2024 |
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BMC Cancer | 2024 |
Tumor-Specific CD8+ T Cells from the Bone Marrow Resist Exhaustion and Exhibit Increased Persistence in Tumor-Bearing Hosts as Compared to Tumor Infiltrating Lymphocytes
Zawidzka EM, Biavati L, Thomas A, Zanettini C, Marchionni L, Leone R, Borrello I |
2023 | |
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Nature Communications | 2021 |
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T cell responses in early-stage melanoma patients occur frequently and are not associated with humoral response
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CD4 + T effector memory cell dysfunction is associated with the accumulation of granulocytic myeloid-derived suppressor cells in glioblastoma patients
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A randomized phase II study of radiation induced immune boost in operable non-small cell lung cancer (RadImmune trial)
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Significance of Heparanase in Cancer and Inflammation
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Intratumoral Immune Responses Can Distinguish New Primary and True Recurrence Types of Ipsilateral Breast Tumor Recurrences (IBTR)
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Randomized controlled phase I/II study to investigate immune stimulatory effects by low dose radiotherapy in primarily operable pancreatic cancer
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BMC Cancer | 2011 |
A randomized controlled trial to investigate the influence of low dose radiotherapy on immune stimulatory effects in liver metastases of colorectal cancer
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Targeting the autophagy pathway for cancer chemoprevention
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BMC Immunology | 2010 |
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Cancer Immunology, Immunotherapy | 2010 |
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Cancer Immunology, Immunotherapy | 2009 |
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Blood | 2009 |
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Cancer Science | 2009 |
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Cancer Immunology, Immunotherapy | 2008 |
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British Journal of Cancer | 2008 |
HLA-A2-Restricted Cytotoxic T Lymphocyte Epitopes from Human Heparanase as Novel Targets for Broad-Spectrum Tumor Immunotherapy
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Neoplasia (New York, N.Y.) | 2008 |
Treatment of advanced metastasized breast cancer with bone marrow-derived tumour-reactive memory T cells: a pilot clinical study
Schuetz F, Ehlert K, Ge Y, Schneeweiss A, Rom J, Inzkirweli N, Sohn C, Schirrmacher V, Beckhove P |
Cancer Immunology, Immunotherapy | 2008 |
Principles of Adoptive T Cell Cancer Therapy
Carl H. June |
Journal of Clinical Investigation | 2007 |
Tumor immunoediting and immunosculpting pathways to cancer progression
JM Reiman, M Kmieciak, MH Manjili, KL Knutson |
Seminars in Cancer Biology | 2007 |
Adoptively transferred human lung tumor specific cytotoxic T cells can control autologous tumor growth and shape tumor phenotype in a SCID mouse xenograft model
E Oflazoglu, M Elliott, H Takita, S Ferrone, RA Henderson, EA Repasky |
Journal of Translational Medicine | 2007 |
Tumor infiltrating T lymphocytes in colorectal cancer: Tumor-selective activation and cytotoxic activity in situ
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Annals of Surgery | 2006 |