Aberrant expression of the hematopoietic-restricted minor histocompatibility antigen LRH-1 on solid tumors results in efficient cytotoxic T cell-mediated lysis.

Abstract

CD8(+) T cells recognizing minor histocompatibility antigens (MiHA) on solid tumor cells may mediate effective graft-versus-tumor (GVT) reactivity after allogeneic stem cell transplantation (SCT). Previously, we identified LRH-1 as a hematopoietic-restricted MiHA encoded by the P2X5 gene. Here, we report that LRH-1 is aberrantly expressed on solid tumor cells. P2X5 mRNA expression is demonstrated in a significant portion of solid tumor cell lines, including renal cell carcinoma (RCC), melanoma, colorectal carcinoma, brain cancer and breast cancer. Importantly, P2X5 gene expression was also detected in a subset of primary solid tumor specimens derived from RCC, brain cancer and breast cancer patients. Furthermore, P2X5 expressing solid tumor cells can be effectively targeted by LRH-1-specific cytotoxic T lymphocytes under inflammatory conditions. The expression of HLA-B7 and CD54 on tumor cells increases upon cytokine stimulation resulting in improved T cell activation as observed by higher levels of degranulation and enhanced tumor cell lysis. Overall, hematopoietic-restricted MiHA LRH-1 is aberrantly expressed on solid tumor cells and may be used as target in GVT-specific immunotherapy after SCT.

• Authors: Ingrid M Overes, T Henriëtte Levenga, Johanna C M Vos, Agnes van Horssen-Zoetbrood, Robbert van der Voort, Pieter H De Mulder, Theo M de Witte, Harry Dolstra
• Journal: Cancer immunology, immunotherapy : CII (Cancer Immunol Immunother) Vol. 58 Issue 3 Pg. 429-39 (Mar 2009) ISSN: 1432-0851 [Electronic] Germany
• PMID: 18719914 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• DNA-Binding Proteins
• Minor Histocompatibility Antigens
• P2RX5 protein, human
• RNA, Messenger
• Receptors, Purinergic P2
• Receptors, Purinergic P2X5
• Transcription Factors
• Intercellular Adhesion Molecule-1

Topics

• CD8-Positive T-Lymphocytes (immunology)
• DNA-Binding Proteins (metabolism, physiology)
• Genotype
• Hematopoietic System (metabolism)
• Humans
• Immunotherapy (methods)
• Intercellular Adhesion Molecule-1 (biosynthesis)
• Microscopy, Fluorescence (methods)
• Minor Histocompatibility Antigens (metabolism)
• Neoplasms (immunology, metabolism)
• RNA, Messenger (metabolism)
• Receptors, Purinergic P2 (metabolism)
• Receptors, Purinergic P2X5
• Stem Cell Transplantation
• T-Lymphocytes (metabolism)
• Transcription Factors (metabolism, physiology)
• Transplantation, Homologous