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THE ROLE OF SPARC IN THE IMMUNE LANDSCAPE OF BLADDER CANCER

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title
THE ROLE OF SPARC IN THE IMMUNE LANDSCAPE OF BLADDER CANCER
author
Hegarty, Abigail
abstract
Bladder cancer (BCa) is an immunogenic disease as the first line of defense fordecades has comprised of BCG coupled with radical cystectomy and immune checkpoint inhibitors have emerged as an attractive treatment option for later stages of BCa. However, few patients can benefit from these treatments and recurrence rates remain high. As immunotherapies function through modulation of the tumor microenvironment, a greater understanding of the bladder cancer immune microenvironment will help improve and advance treatment options. In this study, we sought to investigate the immune landscape regulated by tumor suppressor SPARC in urothelial tumors induced by chemical carcinogen in GEMMs and in bone-marrow derived myeloid (BMDM) and macrophage cells with global Sparc knockdown. We found that mice with urothelial knock-in of Sparc (SparcuroKI) were associated with hot tumors with a noted increase in CD8 tumor infiltrating lymphocytes, whereas urothelial knock-out of Sparc (SparcuroKO) resulted in cold tumors. The results also indicate BMDM cells lacking SPARC polarized to a pro-tumor M2 phenotype expressed greater anti-inflammatory, M2 markers compared to wild-type derived M2 BMDM cells. Additionally, the increased expression of these tumor prompting markers was heightened in female derived BMDM cells. Together, these results indicate the presence of SPARC promotes immune recruitment in the urothelium while in BMDM cells, the absence of SPARC results in magnified polarization to a tumor promoting M2 phenotype.
subject
bladder cancer
cancer
sparc
tumor microenvironment
contributor
Said, Neveen (advisor)
Gmeiner, William (committee member)
Grayson, Jason (committee member)
date
2023-07-25T17:48:45Z (accessioned)
2023 (issued)
degree
Biomedical Science – MS (discipline)
embargo
2024-06-06 (terms)
2024-06-06 (liftdate)
identifier
http://hdl.handle.net/10339/102277 (uri)
language
en (iso)
publisher
Wake Forest University
type
Thesis

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