Aberrant expression of the hematopoietic-restricted minor histocompatibility antigen LRH-1 on solid tumors results in efficient cytotoxic T cell-mediated lysis.
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.
Overes
Ingrid M
IM
Central Hematology Laboratory, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
Levenga
T Henriëtte
TH
Vos
Johanna C M
JC
van Horssen-Zoetbrood
Agnes
A
van der Voort
Robbert
R
De Mulder
Pieter H
PH
de Witte
Theo M
TM
Dolstra
Harry
H
D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D004268:DNA-Binding Proteins / Q000378:metabolism* / Q000502:physiology; D005838:Genotype; D006413:Hematopoietic System / Q000378:metabolism*; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D008856:Microscopy, Fluorescence / Q000379:methods; D015778:Minor Histocompatibility Antigens / Q000378:metabolism*; D009369:Neoplasms / Q000276:immunology* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D018048:Receptors, Purinergic P2 / Q000378:metabolism*; D058485:Receptors, Purinergic P2X5; D033581:Stem Cell Transplantation; D013601:T-Lymphocytes / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism* / Q000502:physiology; D014184:Transplantation, Homologous
D004268:DNA-Binding Proteins; D015778:Minor Histocompatibility Antigens; C546465:P2RX5 protein, human; D012333:RNA, Messenger; D018048:Receptors, Purinergic P2; D058485:Receptors, Purinergic P2X5; D014157:Transcription Factors; D018799:Intercellular Adhesion Molecule-1