Holtan, Shernan
Mayo Clinic
Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA.
Citations 13
Fetal Sex‐Based Differences in Maternal Hormones, Angiogenic Factors, and Immune Mediators During Pregnancy and the Postpartum Period
Enninga, Elizabeth Ann L. , Nevala, Wendy K. , Creedon, Douglas J., Holtan, Shernan G. , Markovic, Svetomir N. , Enninga, Elizabeth Ann L , Holtan, Shernan
American Journal of Reproductive Immunology | August 4, 2014 | Volume: 73 | Issue: 3 | Pages: 251-262
ProblemSeveral pregnancy complications have disparities based on the sex of the fetus. It is unknown whether the sex of the fetus differentially alters the maternal immune milieu, potentially contributing to the observed differences.Method of studyUsing maternal plasma collected during 38 uncomplicated pregnancies (19 males, 19 females), we compared levels of cytokines, sex hormones, and angiogenic factors throughout gestation and postpartum.ResultsMale fetal sex was associated with higher levels of proinflammatory cytokines (G‐CSF, IL‐12p70, IL‐21, and IL‐33) and angiogenic factors (PlGF and VEGF‐A) compared with female fetal sex at multiple timepoints. Female fetal sex was associated with higher levels of regulatory cytokines (IL‐5, IL‐9, IL‐17, and IL‐25). IL‐27 increased throughout pregnancy regardless of fetal sex. There was no fetal sex‐based difference in analyte concentrations at the postpartum measurement.ConclusionWomen carrying a male fetus exhibit a more proinflammatory/proangiogenic immune milieu than women carrying a female fetus.
The Dynamic Human Immune Response to Cancer: it Might Just be Rocket Science
Holtan, Shernan G. , Dronca, Roxana , Nevala, Wendy K. , Porrata, Luis F. , Mansfield, Aaron S. , Block, Matthew S. , Leontovich, Alexey A. , Grotz, Travis E. , Turner, James D. , Frisch, H. P., Markovic, Svetomir N. , Mansfield, Aaron S , Grotz, Travis E , Holtan, Shernan
Immunotherapy | September 13, 2011 | Volume: 3 | Issue: 9 | Pages: 1021-1024
Expansion of CD16-Negative Natural Killer Cells in the Peripheral Blood of Patients with Metastatic Melanoma
Holtan, Shernan G. , Creedon, Douglas J., Nevala, Wendy K. , Thompson, Michael A. , Markovic, Svetomir N. , Holtan, Shernan
Clinical and Developmental Immunology | February 23, 2011 | Volume: 2011 | Issue: No issue available | Pages: 1-6
Altered natural killer (NK) cell function is a component of the global immune dysregulation that occurs in advanced malignancies. Another condition associated with altered NK homeostasis is normal pregnancy, where robust infiltration with CD16− CD9+ NK cells can be identified in decidual tissues, along with a concomitant expansion of CD16− NK cells in the maternal peripheral blood. In metastatic melanoma, we identified a similar expansion of peripheral blood CD16− NK cells (median 7.4% in 41 patients with melanoma compared with 3.0% in 29 controls,P<.001). A subset of NK cells in melanoma patients also expresses CD9, which is characteristically expressed only on NK cells within the female reproductive tract. Expansion of CD16− NK cells was associated with elevated plasma transforming growth factor-beta (TGF-βlevels (median 20 ng/ml, Spearman'sρ=0.81,P=.015)). These findings suggest the possibility of exploring anti-TGF-βtherapy to restore NK function in melanoma.