Natural immunity to pluripotency antigen OCT4 in humans Journal Article
| Authors: | Dhodapkar, K. M.; Feldman, D.; Matthews, P.; Radfar, S.; Pickering, R.; Turkula, S.; Zebroski, H.; Dhodapkar, M. V. |
| Article Title: | Natural immunity to pluripotency antigen OCT4 in humans |
| Abstract: | OCT4 is a transcription factor critical for the pluripotency of human embryonal stem (ES) and induced pluipotency stem (IPS) cells. OCT4 is commonly expressed in germ-cell tumors aswell as putative cancer stem cells in several tumors, and is a key determinant of oncogenic fate in germ-cell tumors. The capacity of the human immune system to recognize this critical stem-cell gene is not known, but has implications for preventing tumors with ES/IPS-based therapies and targeting stem-cell pathways in cancer. Here we show that OCT4-specific T cells can be readily detected in freshly isolated T cells from most (>80%) healthy donors. The reactivity to OCT4-derived peptides resides primarily in the CD45RO+ memory T-cell compartment and consists predominantly of CD4+ T cells. T cells reactive against OCT4-derived peptides can be readily expanded in culture using peptide-loaded dendritic cells. In contrast to healthy donors, immunity to OCT4 was detected in only 35% of patients with newly diagnosed germ-cell tumors. However, chemotherapy of germ-cell tumors led to the induction of anti-OCT4 immunity in vivo in patients lacking such responses at baseline. These data demonstrate the surprising lack of immune tolerance to this critical pluripotency antigen in humans. Harnessing natural immunity to this antigen may allow immune-based targeting of pluripotency-related pathways for prevention of cancers, including those in the setting of ES/IPS-based therapies. |
| Keywords: | cancer chemotherapy; cell proliferation; t lymphocyte; t-lymphocytes; dendritic cell; lymphocyte activation; dendritic cells; antigens; leukocytes, mononuclear; cd4+ t lymphocyte; tumor immunity; innate immunity; immunity, innate; testicular cancer; neoplasms, germ cell and embryonal; pluripotent stem cell; pluripotent stem cells; germ cell tumor; cell separation; octamer transcription factor 4; octamer transcription factor-3; immunologic memory; blood donors; cancer stem cells; embryonal stem cells; cd45ro antigen |
| Journal Title: | Proceedings of the National Academy of Sciences of the United States of America |
| Volume: | 107 |
| Issue: | 19 |
| ISSN: | 0027-8424 |
| Publisher: | National Academy of Sciences |
| Date Published: | 2010-05-11 |
| Start Page: | 8718 |
| End Page: | 8723 |
| Language: | English |
| DOI: | 10.1073/pnas.0915086107 |
| PUBMED: | 20404147 |
| PROVIDER: | scopus |
| PMCID: | PMC2889362 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 3" - "Export Date: 20 April 2011" - "CODEN: PNASA" - "Source: Scopus" |
Altmetric
Citation Impact
BMJ Impact Analytics
Related MSK Work