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Expression and T cell Regulatory Action of the PD-1 Immune Checkpoint in the Ovary and Fallopian Tube

View ORCID ProfileJoshua Johnson, Peter Ka Sam, Rengasamy Asokan, Evelyn Llerena Cari, Elise S. Bales, Thanh-Ha Luu, Lauren Perez, Amanda N. Kallen, Liesl Nel-Themaat, Alex J. Polotsky, Miriam D. Post, David J. Orlicky, Kimberly R. Jordan, View ORCID ProfileBenjamin G. Bitler
doi: https://doi.org/10.1101/2020.06.06.138123
Joshua Johnson
1University of Colorado Anschutz Medical Campus, Department of Obstetrics and Gynecology, Division of Reproductive Sciences, Building RC2, Room P15 3103, Mail Stop 8613, Aurora, Colorado 80045
2University of Colorado Anschutz Medical Campus, Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology and Infertility, 12631 East 17th Avenue, Room 4409, B198-3 Aurora, Colorado 80045
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  • For correspondence: joshua.2.johnson@ucdenver.edu
Peter Ka Sam
3University of Colorado-Boulder
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Rengasamy Asokan
1University of Colorado Anschutz Medical Campus, Department of Obstetrics and Gynecology, Division of Reproductive Sciences, Building RC2, Room P15 3103, Mail Stop 8613, Aurora, Colorado 80045
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Evelyn Llerena Cari
1University of Colorado Anschutz Medical Campus, Department of Obstetrics and Gynecology, Division of Reproductive Sciences, Building RC2, Room P15 3103, Mail Stop 8613, Aurora, Colorado 80045
2University of Colorado Anschutz Medical Campus, Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology and Infertility, 12631 East 17th Avenue, Room 4409, B198-3 Aurora, Colorado 80045
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Elise S. Bales
1University of Colorado Anschutz Medical Campus, Department of Obstetrics and Gynecology, Division of Reproductive Sciences, Building RC2, Room P15 3103, Mail Stop 8613, Aurora, Colorado 80045
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Thanh-Ha Luu
1University of Colorado Anschutz Medical Campus, Department of Obstetrics and Gynecology, Division of Reproductive Sciences, Building RC2, Room P15 3103, Mail Stop 8613, Aurora, Colorado 80045
2University of Colorado Anschutz Medical Campus, Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology and Infertility, 12631 East 17th Avenue, Room 4409, B198-3 Aurora, Colorado 80045
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Lauren Perez
4University of California-Los Angeles
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Amanda N. Kallen
5Yale School of Medicine, Department of Obstetrics & Gynecology
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Liesl Nel-Themaat
2University of Colorado Anschutz Medical Campus, Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology and Infertility, 12631 East 17th Avenue, Room 4409, B198-3 Aurora, Colorado 80045
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Alex J. Polotsky
1University of Colorado Anschutz Medical Campus, Department of Obstetrics and Gynecology, Division of Reproductive Sciences, Building RC2, Room P15 3103, Mail Stop 8613, Aurora, Colorado 80045
2University of Colorado Anschutz Medical Campus, Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology and Infertility, 12631 East 17th Avenue, Room 4409, B198-3 Aurora, Colorado 80045
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Miriam D. Post
1University of Colorado Anschutz Medical Campus, Department of Obstetrics and Gynecology, Division of Reproductive Sciences, Building RC2, Room P15 3103, Mail Stop 8613, Aurora, Colorado 80045
6University of Colorado Anschutz Medical Campus, Department of Pathology, Mailstop F768, 12605 East 16th Avenue, Aurora, Colorado 80045
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David J. Orlicky
1University of Colorado Anschutz Medical Campus, Department of Obstetrics and Gynecology, Division of Reproductive Sciences, Building RC2, Room P15 3103, Mail Stop 8613, Aurora, Colorado 80045
6University of Colorado Anschutz Medical Campus, Department of Pathology, Mailstop F768, 12605 East 16th Avenue, Aurora, Colorado 80045
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Kimberly R. Jordan
7University of Colorado Anschutz Medical Campus, Department of Immunology and Microbiology, Human Immunology and Immunotherapy Initiative, Human Immune Monitoring Shared Resource, RC1-North, 8113, Aurora, Colorado 80045
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Benjamin G. Bitler
1University of Colorado Anschutz Medical Campus, Department of Obstetrics and Gynecology, Division of Reproductive Sciences, Building RC2, Room P15 3103, Mail Stop 8613, Aurora, Colorado 80045
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  • ORCID record for Benjamin G. Bitler
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Abstract

The Programmed Cell Death Protein-1 (PD-1/PDCD-1/CD279) checkpoint has powerful immunomodulatory action, including in the context of cancer. PD-1 receptor activation by its ligands (PD-L1/2) is associated with downregulated immune response, and tumor cells can avoid surveillance via PD-1 and/or ligand expression. While receptor expression is largely limited to lymphoid, myeloid, and tumor cells, we show that membrane bound and soluble variants of PD-1 and ligands are also expressed by permanent constituent cell types of the human ovary and fallopian tube, including granulosa cells and oocytes. PD-1 and soluble ligands were highly enriched in exosome fractions in human follicular fluid at bioactive levels that can control T cell PD-1 activation. PD-1 checkpoint signaling may be involved in physiological ovarian functions including follicle, and ultimately, germline and embryo immune-privilege.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted June 07, 2020.
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Expression and T cell Regulatory Action of the PD-1 Immune Checkpoint in the Ovary and Fallopian Tube
Joshua Johnson, Peter Ka Sam, Rengasamy Asokan, Evelyn Llerena Cari, Elise S. Bales, Thanh-Ha Luu, Lauren Perez, Amanda N. Kallen, Liesl Nel-Themaat, Alex J. Polotsky, Miriam D. Post, David J. Orlicky, Kimberly R. Jordan, Benjamin G. Bitler
bioRxiv 2020.06.06.138123; doi: https://doi.org/10.1101/2020.06.06.138123
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Expression and T cell Regulatory Action of the PD-1 Immune Checkpoint in the Ovary and Fallopian Tube
Joshua Johnson, Peter Ka Sam, Rengasamy Asokan, Evelyn Llerena Cari, Elise S. Bales, Thanh-Ha Luu, Lauren Perez, Amanda N. Kallen, Liesl Nel-Themaat, Alex J. Polotsky, Miriam D. Post, David J. Orlicky, Kimberly R. Jordan, Benjamin G. Bitler
bioRxiv 2020.06.06.138123; doi: https://doi.org/10.1101/2020.06.06.138123

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