CSPG4 Expression in GIST Is Associated with Better Prognosis and Strong Cytotoxic Immune Response.
CAR-CIKs
CSPG4
GIST
NK cells
gene expression
immune response
prognosis
Journal
Cancers
ISSN: 2072-6694
Titre abrégé: Cancers (Basel)
Pays: Switzerland
ID NLM: 101526829
Informations de publication
Date de publication:
03 Mar 2022
03 Mar 2022
Historique:
received:
28
01
2022
revised:
28
02
2022
accepted:
02
03
2022
entrez:
10
3
2022
pubmed:
11
3
2022
medline:
11
3
2022
Statut:
epublish
Résumé
The treatment of gastrointestinal stromal tumors (GIST) must be improved through the development of more reliable prognostic factors and of therapies able to overcome imatinib resistance. The immune system represents an attractive tool. CSPG4, a cell surface proteoglycan, emerged as a potential therapeutic target for immune therapy in different cancers, including cell therapy based on CSPG4-specific chimeric antigen receptor (CAR)-redirected cytokine-induced killer lymphocytes (CSPG4-CAR.CIKs) in sarcomas. CSPG4 expression has never been studied in GIST. We analyzed CSPG4 mRNA expression data of 309 clinical GIST samples profiled using DNA microarrays and searched for correlations with clinicopathological and immune features. CSPG4 expression, higher in tumors than normal digestive tissues, was heterogeneous across tumors. High expression was associated with AFIP low-risk, gastric site, and localized stage, and independently with longer postoperative disease-free survival (DFS) in localized stage. The correlations between CSPG4 expression and immune signatures highlighted a higher anti-tumor immune response in "CSPG4-high" tumors, relying on both the adaptive and innate immune system, in which the boost of NK cells by CSPG4-CAR.CIKs might be instrumental, eventually combined with immune checkpoint inhibitors. In conclusion, high CSPG4 expression in GIST is associated with better DFS and offers an immune environment favorable to a vulnerability to CAR.CIKs.
Identifiants
pubmed: 35267618
pii: cancers14051306
doi: 10.3390/cancers14051306
pmc: PMC8909029
pii:
doi:
Types de publication
Journal Article
Langues
eng
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