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@ARTICLE{Brummer:278578,
author = {T. Brummer$^*$ and R. Zeiser$^*$},
title = {{T}he role of the {MDM}2/p53 axis in anti-tumor immune
responses},
journal = {Blood},
volume = {143},
number = {26},
issn = {0006-4971},
address = {Washington, DC},
publisher = {American Society of Hematology},
reportid = {DKFZ-2023-01659},
pages = {2701-2709},
year = {2024},
note = {2024 Jun 27;143(26):2701-2709},
abstract = {Mouse double minute 2 homolog (MDM2) is a negative
regulator of the tumor suppressor p53 and often highly
expressed in acute myeloid leukemia (AML) and different
solid tumors. Inactivating mutations in TP53, the gene
encoding for p53, confers an unfavorable prognosis in AML
and increases the risk for relapse after allogeneic
hematopoietic cell transplantation (allo-HCT). We review the
concept that manipulation of MDM2 and p53 could enhance
immunogenicity of AML and solid tumor cells. Additionally,
we discuss the mechanisms by which MDM2 and p53 regulate MHC
class I and II expression, transcription of dsRNA of
endogenous retroviruses, interferon responses, IL-15
production and TRAIL-receptor 1 and 2 expression on
malignant cells. The direct effects of MDM2-inhibition or
MDM2 deletion in effector T cells are discussed in the
context of cancer immunotherapy. The preclinical findings
are connected to clinical studies using MDM2-inhibition to
enhance anti-tumor immunity in patients. In aggregate, this
review summarizes current evidence supporting the use of
MDM2-inhibition to restore p53, as well as direct effects of
MDM2-inhibition on T cells as an emerging concept for
combined anti-tumor immunotherapy against hematological
malignancies and beyond.},
subtyp = {Review Article},
cin = {FR01},
ddc = {610},
cid = {I:(DE-He78)FR01-20160331},
pnm = {899 - ohne Topic (POF4-899)},
pid = {G:(DE-HGF)POF4-899},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:37467495},
doi = {10.1182/blood.2023020731},
url = {https://inrepo02.dkfz.de/record/278578},
}