Stress, the Immune System and Basal Cell Carcinoma

Summary

Principal Investigator: RONALD M GLASER
Abstract: Skin cancer, the most common cancer in the U.S., is more prevalent than all other malignancies combined. Basal cell carcinoma (BCC), the most common form of human cancer, shows evidence for spontaneous regression in approximately 44% of the tumors. Importantly, both spontaneous regression of tumors and appearance of new tumors appear to be related to the immune response to the tumor. Focusing on the microenvironment within BCC tumors, this study addresses the interplay between psychological factors and immune function, and how this interplay may be related to immune/molecular markers associated with histopathological characteristics of BCC tumors that are relatively higher or lower in their immunoreactivity. We will recruit 320 patients who have recently had a BCC removed (the "index" tumor). Two pathologists will evaluate the tumors and assess their immunoreactivity as measured by the level of immune cells trafficking to the tumor and the expression of immune and apoptotic markers expressed by these cells; they will also determine the tumor subtype. We will evaluate cross-sectional relationships between the immunogenic status of the BCC tumors and the influence of age, gender, severe life stressors, and depressive symptoms. Accordingly, we have the following specific aims: 1) Using the index BCC, we will determine if depressive symptoms and severe life stressors are related to markers shown to be reflective of immunoreactivity to a BCC, i.e., tumors showing differences in the level of CD3+ and CD68+ cells that traffic to the BCC tumor and surrounding stroma (quantitative measures) and the expression of cell markers, including CD25, ICAM-1, IFN-7, and IL-10, reflecting the activation of these cells (qualitative measures) and bcl-2, an apoptosis marker associated with tumor regression. 2) We will determine if the relationships between depressive symptoms and severe life stressors and tumor immunoreactivity are more pronounced among older adults.
Funding Period: 2005-03-16 - 2008-02-28
more information: NIH RePORT

Top Publications

  1. pmc Gender specific association of child abuse and adult cardiovascular disease in a sample of patients with basal cell carcinoma
    Georgina M Hosang
    MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King s College London, De Crespigny Park, London SE5 8AF, UK
    Child Abuse Negl 37:374-9. 2013
  2. pmc Basal cell carcinoma: stressful life events and the tumor environment
    Christopher P Fagundes
    Institute for Behavioral Medicine Research, The Ohio State University Medical Center, Columbus, OH 43210, USA
    Arch Gen Psychiatry 69:618-26. 2012
  3. pmc Tumor site immune markers associated with risk for subsequent basal cell carcinomas
    Ronald Glaser
    Institute for Behavioral Medicine Research, The Ohio State University Medical Center, Columbus, Ohio, United States of America
    PLoS ONE 6:e25160. 2011
  4. pmc Glucocorticoids activate Epstein Barr virus lytic replication through the upregulation of immediate early BZLF1 gene expression
    Eric V Yang
    Institute for Behavioral Medicine Research, The Ohio State University Medical Center, 460 Medical Center Drive, Columbus, OH 43210, USA
    Brain Behav Immun 24:1089-96. 2010
  5. pmc Norepinephrine upregulates VEGF, IL-8, and IL-6 expression in human melanoma tumor cell lines: implications for stress-related enhancement of tumor progression
    Eric V Yang
    Department of Molecular Virology, Immunology and Medical Genetics, The Ohio State University Medical Center, Columbus, OH 43210, USA
    Brain Behav Immun 23:267-75. 2009
  6. pmc VEGF is differentially regulated in multiple myeloma-derived cell lines by norepinephrine
    Eric V Yang
    Department of Molecular Virology, Immunology and Medical Genetics, The Ohio State University Medical Center, Columbus, OH 43210, USA
    Brain Behav Immun 22:318-23. 2008
  7. pmc Chronic herpesvirus reactivation occurs in aging
    Raymond P Stowe
    Department of Pathology, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555, United States
    Exp Gerontol 42:563-70. 2007
  8. ncbi Norepinephrine up-regulates the expression of vascular endothelial growth factor, matrix metalloproteinase (MMP)-2, and MMP-9 in nasopharyngeal carcinoma tumor cells
    Eric V Yang
    Department of Molecular Virology, The Ohio State University Medical Center, Columbus, OH 43210, USA
    Cancer Res 66:10357-64. 2006
  9. pmc Stress, age, and immune function: toward a lifespan approach
    Jennifer E Graham
    Department of Molecular Virology, Immunology, and Medical Genetics, The Ohio State University College of Medicine, Columbus, OH 43210, USA
    J Behav Med 29:389-400. 2006

Scientific Experts

  • Ronald Glaser
  • Jennifer E Graham
  • Raymond Stowe
  • Eric V Yang
  • Min Chen
  • Georgina M Hosang
  • Mark A Bechtel
  • David R Lambert
  • Joel B Herron
  • Sheri L Johnson
  • Michael P Di Gregorio
  • Dean W Hearne
  • Christopher P Fagundes
  • Jeanette I Webster Marketon
  • Seung Jae Kim
  • Elise L Donovan
  • Janice Kiecolt-Glaser
  • Janice K Kiecolt-Glaser
  • Rebecca R Andridge
  • Scott D Jewell
  • Kwok Wai Lo
  • Amy C Gross
  • Sanford H Barsky
  • Don M Benson
  • Carl Morrison
  • Tim D Eubank
  • Nicholas A Flavahan
  • Peir En Yeh
  • Clay B Marsh
  • Yang Li
  • Anil K Sood
  • Stanley Lemeshow
  • Scott Jewell

Detail Information

Publications10

  1. pmc Gender specific association of child abuse and adult cardiovascular disease in a sample of patients with basal cell carcinoma
    Georgina M Hosang
    MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King s College London, De Crespigny Park, London SE5 8AF, UK
    Child Abuse Negl 37:374-9. 2013
    ..The aim of this study is to examine whether child abuse or neglect is more strongly associated with adult cardiovascular disease, and whether these associations differ by gender...
  2. pmc Basal cell carcinoma: stressful life events and the tumor environment
    Christopher P Fagundes
    Institute for Behavioral Medicine Research, The Ohio State University Medical Center, Columbus, OH 43210, USA
    Arch Gen Psychiatry 69:618-26. 2012
    ..Basal cell carcinoma (BCC) is the most common skin cancer, and the immune system plays a prominent role in tumor appearance and progression...
  3. pmc Tumor site immune markers associated with risk for subsequent basal cell carcinomas
    Ronald Glaser
    Institute for Behavioral Medicine Research, The Ohio State University Medical Center, Columbus, Ohio, United States of America
    PLoS ONE 6:e25160. 2011
    ..Basal cell carcinoma (BCC) tumors are the most common skin cancer and are highly immunogenic...
  4. pmc Glucocorticoids activate Epstein Barr virus lytic replication through the upregulation of immediate early BZLF1 gene expression
    Eric V Yang
    Institute for Behavioral Medicine Research, The Ohio State University Medical Center, 460 Medical Center Drive, Columbus, OH 43210, USA
    Brain Behav Immun 24:1089-96. 2010
    ..The results suggest that GCs, in addition to inducing stress-related immune dysregulation, can mediate latent EBV reactivation through the induction of the BZLF1 gene...
  5. pmc Norepinephrine upregulates VEGF, IL-8, and IL-6 expression in human melanoma tumor cell lines: implications for stress-related enhancement of tumor progression
    Eric V Yang
    Department of Molecular Virology, Immunology and Medical Genetics, The Ohio State University Medical Center, Columbus, OH 43210, USA
    Brain Behav Immun 23:267-75. 2009
    ....
  6. pmc VEGF is differentially regulated in multiple myeloma-derived cell lines by norepinephrine
    Eric V Yang
    Department of Molecular Virology, Immunology and Medical Genetics, The Ohio State University Medical Center, Columbus, OH 43210, USA
    Brain Behav Immun 22:318-23. 2008
    ..The data suggest that the ability of NE to regulate the expression of VEGF is not limited to solid epithelial tumors and suggests a possible regulatory role of catecholamine stress hormones in MM progression...
  7. pmc Chronic herpesvirus reactivation occurs in aging
    Raymond P Stowe
    Department of Pathology, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555, United States
    Exp Gerontol 42:563-70. 2007
    ..These findings indicate that the aged immune system is no longer able to control EBV and CMV reactivation that could now be characterized as chronic instead of latent...
  8. ncbi Norepinephrine up-regulates the expression of vascular endothelial growth factor, matrix metalloproteinase (MMP)-2, and MMP-9 in nasopharyngeal carcinoma tumor cells
    Eric V Yang
    Department of Molecular Virology, The Ohio State University Medical Center, Columbus, OH 43210, USA
    Cancer Res 66:10357-64. 2006
    ..The data suggest that catecholamine hormones produced by the sympathetic-adrenal medullary axis may affect NPC tumor progression, in part, through modulation of key angiogenic cytokines...
  9. pmc Stress, age, and immune function: toward a lifespan approach
    Jennifer E Graham
    Department of Molecular Virology, Immunology, and Medical Genetics, The Ohio State University College of Medicine, Columbus, OH 43210, USA
    J Behav Med 29:389-400. 2006
    ..An understanding of the interactive effects of stress and age is critical to efforts to determine underlying mechanisms, clarify the directionality of effects, and develop effective interventions in early and late life...