Immunological Mechanisms of Extracorporeal Photopheresis In Cutaneous T Cell Lymphoma and Graft Versus Host Disease

<p><strong>IMMUNOLOGICAL MECHANISMS OF EXTRACORPOREAL PHOTOPHERESIS IN CUTANEOUS T CELL LYMPHOMA AND GRAFT VERSUS HOST DISEASE</strong></p> <p>Publication No.___________</p> <p>Lisa Harn-Ging Shiue, B.S.</p> <p>Supervisory Professor: Madeleine Duvic, M.D.</p> <p>Extracorporeal photopheresis (ECP) is an effective, low-risk immunomodulating therapy for leukemic cutaneous T cell lymphoma (L-CTCL) and graft versus host disease (GVHD), but whether the mechanism(s) of action in these two diseases is (are) identical or different is unclear. To determine the effects of ECP <em>in vivo</em>, we studied regulatory T cells (T-regs), cytotoxic T lymphocytes (CTLs), and dendritic cells (DCs) by immunofluorescence flow cytometry in 18 L-CTCL and 11 GVHD patients before and after ECP at Day 2, 1 month, 3 months, and 6 months. In this study, ECP was effective in 12/18 L-CTCL patients with a 66.7% overall response rate (ORR) and 6/11 GVHD patients with a 54.5% ORR. Prior to ECP, the percentages of CD4⁺Foxp3⁺ T cells in 9 L-CTCL patients were either lower (L-CTCL-Low, n=2) or higher (L-CTCL-High, n=7) than normal. Five of the 7 GVHD patients had high percentages of CD4⁺Foxp3⁺ T cells (GVHD-High). Six of 7 L-CTCL-High patients had >80% CD4⁺Foxp3⁺ T cells which were correlated with tumor cells, and were responders. Both L-CTCL-High and GVHD-High patients had decreased percentages of CD4⁺Foxp3⁺ and CD4⁺Foxp3⁺CD25^- T cells after 3 months of treatment. CD4⁺Foxp3⁺CD25⁺ T cells increased in GVHD-High patients but decreased in L-CTCL-High patients after 3 months of ECP. In addition, numbers of CTLs were abnormal. We confirmed that numbers of CTLs were low in L-CTCL patients, but high in GVHD patients prior to ECP. After ECP, CTLs increased after 1 month in 4/6 L-CTCL patients whereas CTLs decreased after 6 months in 3/3 GVHD patients. Myeloid (mDCs) and plasmacytoid DCs (pDCs) were also low at baseline in L-CTCL and GVHD patients confirming the DC defect. After 6 months of ECP, numbers and percentages of mDCs and pDCs increased in L-CTCL and GVHD. MDCs were favorably increased in 8/12 L-CTCL responders whereas pDCs were favorably increased in GVHD patients. These data suggest that ECP is favorably modulating the DC subsets. In L-CTCL patients, the mDCs may orchestrate Th1 cell responses to overcome immune suppression and facilitate disease regression. However, in GVHD patients, ECP is favorably down-regulating the immune system and may be facilitating immune tolerance to auto-or allo-antigens. In both L-CTCL and GVHD patients, DCs are modulated, but the T cell responses orchestrated by the DCs are different, suggesting that ECP modulates depending on the immune milieu.</p> <p>_______________</p>

Name thesis:degree_name

Doctor of Philosophy (PhD)

Level thesis:degree_level

Dissertation (PhD)

Year dc:date.available

2012

Author dc:creator

• Shiue, Lisa

Contributors dc:contributor

• Madeleine Duvic, M.D.
• Amin Alousi, M.D.
• Wei Cao, Ph.D.

• Immunobiology
• regulatory T cells
• cytotoxic T lymphocytes
• dendritic cells
• humans
• Houston
• TX
• UT MD Anderson Cancer Center
• Immunopathology
• Immunoprophylaxis and Therapy
• Medicine and Health Sciences
• Other Immunology and Infectious Disease

Repository record dc:identifier

https://digitalcommons.library.tmc.edu/utgsbs_dissertations/327

OAI identifier oai:identifier

oai:digitalcommons.library.tmc.edu:utgsbs_dissertations-1362