The role of macrophages in non-small cell lung cancer and advancements in 3D co-cultures.
NSCLC
cancer biology
co-culture
lung cancer
macrophages
organoids
Journal
eLife
ISSN: 2050-084X
Titre abrégé: Elife
Pays: England
ID NLM: 101579614
Informations de publication
Date de publication:
21 02 2023
21 02 2023
Historique:
received:
02
11
2022
accepted:
09
02
2023
pubmed:
23
2
2023
medline:
25
2
2023
entrez:
22
2
2023
Statut:
epublish
Résumé
Lung cancer (LC) is the leading cause of cancer-related deaths worldwide. Traditional therapeutic approaches such as chemotherapy or radiotherapy have provided only a marginal improvement in the treatment of lung carcinomas. Inhibitors targeting specific genetic aberrations present in non-small cell lung cancer (NSCLC), the most common subtype (85%), have improved the prognostic outlook, but due to the complexity of the LC mutational spectrum, only a fraction of patients benefit from these targeted molecular therapies. More recently, the realization that the immune infiltrate surrounding solid tumors can foster tumor-promoting inflammation has led to the development and implementation of anticancer immunotherapies in the clinic. In NSCLC, one of the most abundant leukocyte infiltrates is macrophages. These highly plastic phagocytes, which are part of the cellular repertoire of the innate immunity, can have a pivotal role in early NSCLC establishment, malignant progression, and tumor invasion. Emerging macrophage-targeting therapies have been focused on the re-differentiation of the macrophages toward an antitumorigenic phenotype, depletion of tumor-promoting macrophage subtypes, or combination therapies combining traditional cytotoxic treatments with immunotherapeutic agents. The most extensively used models employed for the exploration of NSCLC biology and therapy have been 2D cell lines and murine models. However, studying cancer immunology requires appropriately complex models. 3D platforms, including organoid models, are quickly advancing powerful tools to study immune cell-epithelial cell interactions within the tumor microenvironment. Co-cultures of immune cells along with NSCLC organoids allow for an in vitro observation of the tumor microenvironment dynamics closely resembling in vivo settings. Ultimately, the implementation of 3D organoid technology into tumor microenvironment-modeling platforms might facilitate the exploration of macrophage-targeted therapies in NSCLC immunotherapeutic research, thus establishing a new frontier in NSCLC treatment.
Identifiants
pubmed: 36809334
doi: 10.7554/eLife.82998
pii: 82998
pmc: PMC9943070
doi:
pii:
Substances chimiques
Antineoplastic Agents
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2023, Baláž, Baláž, Balážová et al.
Déclaration de conflit d'intérêts
KB, AD No competing interests declared, HC is inventor on patents, owned by the Royal Netherlands Academy of Sciences and related to organoid research. The relevant International Application Numbers are: PCT/NL2008/050543 (Publication Number WO2009/022907) and PCT/NL2010/000017 (Publication Number WO2010/090513). Furthermore, HC is currently employed by Roche (Basel, Switzerland) as head of Pharma Research and Early Development. His full disclosure: www.uu.nl/staff/JCClevers/Additional
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