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@ARTICLE{Horvat:289486,
author = {N. K. Horvat and S. Chocarro$^*$ and O. Marques and T. A.
Bauer and R. Qiu and A. Diaz-Jimenez$^*$ and B. Helm$^*$ and
Y. Chen$^*$ and S. Sawall$^*$ and R. Sparla and L. Su and U.
Klingmüller$^*$ and M. Barz and M. W. Hentze and R.
Sotillo$^*$ and M. U. Muckenthaler},
title = {{S}uperparamagnetic {I}ron {O}xide {N}anoparticles
{R}eprogram the {T}umor {M}icroenvironment and {R}educe
{L}ung {C}ancer {R}egrowth after {C}rizotinib {T}reatment.},
journal = {ACS nano},
volume = {18},
number = {17},
issn = {1936-0851},
address = {Washington, DC},
publisher = {Soc.},
reportid = {DKFZ-2024-00808},
pages = {11025-11041},
year = {2024},
note = {#LA:B220# / 2024 Apr 30;18(17):11025-11041},
abstract = {ALK-positive NSCLC patients demonstrate initial responses
to ALK tyrosine kinase inhibitor (TKI) treatments, but
eventually develop resistance, causing rapid tumor relapse
and poor survival rates. Growing evidence suggests that the
combination of drug and immune therapies greatly improves
patient survival; however, due to the low immunogenicity of
the tumors, ALK-positive patients do not respond to
currently available immunotherapies. Tumor-associated
macrophages (TAMs) play a crucial role in facilitating lung
cancer growth by suppressing tumoricidal immune activation
and absorbing chemotherapeutics. However, they can also be
programmed toward a pro-inflammatory tumor suppressive
phenotype, which represents a highly active area of therapy
development. Iron loading of TAMs can achieve such
reprogramming correlating with an improved prognosis in lung
cancer patients. We previously showed that superparamagnetic
iron oxide nanoparticles containing core-cross-linked
polymer micelles (SPION-CCPMs) target macrophages and
stimulate pro-inflammatory activation. Here, we show that
SPION-CCPMs stimulate TAMs to secrete reactive nitrogen
species and cytokines that exert tumoricidal activity. We
further show that SPION-CCPMs reshape the immunosuppressive
Eml4-Alk lung tumor microenvironment (TME) toward a
cytotoxic profile hallmarked by the recruitment of CD8+ T
cells, suggesting a multifactorial benefit of SPION-CCPM
application. When intratracheally instilled into lung
cancer-bearing mice, SPION-CCPMs delay tumor growth and,
after first line therapy with a TKI, halt the regrowth of
relapsing tumors. These findings identify SPIONs-CCPMs as an
adjuvant therapy, which remodels the TME, resulting in a
delay in the appearance of resistant tumors.},
keywords = {adjuvant therapy (Other) / iron homeostasis (Other) / lung
cancer (Other) / nanoparticle (Other) / polymeric micelle
(Other)},
cin = {B220 / HD01 / B200 / E025},
ddc = {540},
cid = {I:(DE-He78)B220-20160331 / I:(DE-He78)HD01-20160331 /
I:(DE-He78)B200-20160331 / I:(DE-He78)E025-20160331},
pnm = {312 - Funktionelle und strukturelle Genomforschung
(POF4-312)},
pid = {G:(DE-HGF)POF4-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:38626916},
doi = {10.1021/acsnano.3c08335},
url = {https://inrepo02.dkfz.de/record/289486},
}