Blockade of the Immune Checkpoint CD47 by TTI-621 Potentiates the Response to Anti-PD-L1 in Cutaneous T-Cell Lymphoma.

ABSTRACT: Cutaneous T-cell lymphoma (CTCL) is an incurable and cosmetically disfiguring disease associated with microenvironmental signals. We investigated the effects of CD47 and PD-L1 immune checkpoint blockades, as a strategy for targeting both innate and adaptive immunity. CIBERSORT analysis identified the immune-cell composition in the CTCL tumor microenvironment and the immune checkpoint expression profile for each immune-cell gene cluster from CTCL lesions. We investigated the relationship between MYC and CD47 and PD-L1 expression and found that MYC short hairpin RNA knockdown and MYC functional suppression by TTI-621 (SIRPαFc) and anti-PD-L1 (durvalumab) in CTCL cell lines reduced the expression of CD47 and PDL1 mRNA and protein as measured by qPCR and flow cytometry, respectively. In vitro,

SUBMITTER: Han Z 

PROVIDER: S-EPMC10363206 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature