Targeting immunosuppression in LAM
Awardee: Yan Tang
Institution: Brigham and Women's Hospital, Harvard Medical School
Grant Amount: $71,051.00
Funding Period: February 1, 2024 - January 31, 2025
Summary:
Lymphangioleiomyomatosis (LAM), pulmonary manifestation of TSC, is a destructive and often fatal lung disease of women, which can lead to lung failure and the need for lung transplantation. LAM can occur as an isolated disorder (sporadic LAM) or in association with TSC. TSC-LAM patients often have angiomyolipoma (AML), the kidney manifestation of TSC. About 60% of sporadic LAM patients also have AML. It seems that LAM and AML share same genetic mutations. We performed single cell analysis on five LAM lungs and six AML specimens and found that subsets of candidate TSC-deficient cells exhibit elevated stemness and dormancy transcriptional programs in both LAM and AML. TSC diseases also exhibit an altered immune microenvironment. We have analyzed adjacent normal kidney tissues for four of the six AML specimens and found that AML tumors are enriched with dysfunctional T cells compared to paired normal kidney. In depth analysis further revealed that stemness-dominant samples are deprived of proliferating T cells, key component in immune system to control tumor growth. In this project, we will investigate how the stemness state of TSC-deficient cells affects immune microenvironment in LAM and assess whether targeting tumor stemness can rejuvenate T cells to better control LAM development.