Macrophages-based immune-related risk score model for relapse prediction in stage I-III non-small cell lung cancer assessed by multiplex immunofluorescence.
Non-small cell lung cancer (NSCLC)
immune-related risk score
random forest algorithm
tumor microenvironment
tumor-associated macrophages
Journal
Translational lung cancer research
ISSN: 2218-6751
Titre abrégé: Transl Lung Cancer Res
Pays: China
ID NLM: 101646875
Informations de publication
Date de publication:
Apr 2022
Apr 2022
Historique:
received:
17
11
2021
accepted:
06
03
2022
entrez:
9
5
2022
pubmed:
10
5
2022
medline:
10
5
2022
Statut:
ppublish
Résumé
Macrophages are critical players in regulating innate and adaptive immunity in the tumor microenvironment (TME). The prognostic value of macrophages and their heterogeneous phenotypes in non-small cell lung cancer (NSCLC) is still uncertain. Surgically-resected samples of 681 NSCLC cases were stained by multiplex immunofluorescence to examine macrophage phenotypes as well as the expression levels of program death-ligand 1 (PD-L1) on them in both tumor nest and tumor stroma, including pan-macrophage (CD68+), M1 (CD68+CD163-), and M2 macrophages (CD68+CD163+). Various other immune cell markers, including CD4, CD8, CD20, CD38, CD66B, FOXP3, and CD133, were also evaluated. Machine learning algorithm by Random Forest (RF) model was utilized to screen the robust prognostic markers and construct the CD68-based immune-related risk score (IRRS) for predicting disease-free survival (DFS). The expression levels of CD68 were moderately correlated with the levels of PD-L1 (P<0.001), CD133 (P<0.001), and CD8 (P<0.001). Higher levels of CD68 (OR 1.03, 95% CI: 1.01-1.05, P<0.001) as well as M1 macrophage (OR 1.04, 95% CI: 1.01-1.06, P<0.001) indicated shorter DFS. Despite without statiscial significance, intratumoral M2 macrophage (OR 1.05, 95% CI: 0.99-1.10, P=0.081) was also associated with worse DFS. IRRS incorporating three intratumoral CD68-related markers and four intrastromal markers was constructed and validated to predict recurrence (high-risk group Our study suggested close interactions between CD68 and other immune markers in TME, demonstrating the prognostic value of CD68 in relapse prediction in resectable NSCLC.
Sections du résumé
Background
UNASSIGNED
Macrophages are critical players in regulating innate and adaptive immunity in the tumor microenvironment (TME). The prognostic value of macrophages and their heterogeneous phenotypes in non-small cell lung cancer (NSCLC) is still uncertain.
Methods
UNASSIGNED
Surgically-resected samples of 681 NSCLC cases were stained by multiplex immunofluorescence to examine macrophage phenotypes as well as the expression levels of program death-ligand 1 (PD-L1) on them in both tumor nest and tumor stroma, including pan-macrophage (CD68+), M1 (CD68+CD163-), and M2 macrophages (CD68+CD163+). Various other immune cell markers, including CD4, CD8, CD20, CD38, CD66B, FOXP3, and CD133, were also evaluated. Machine learning algorithm by Random Forest (RF) model was utilized to screen the robust prognostic markers and construct the CD68-based immune-related risk score (IRRS) for predicting disease-free survival (DFS).
Results
UNASSIGNED
The expression levels of CD68 were moderately correlated with the levels of PD-L1 (P<0.001), CD133 (P<0.001), and CD8 (P<0.001). Higher levels of CD68 (OR 1.03, 95% CI: 1.01-1.05, P<0.001) as well as M1 macrophage (OR 1.04, 95% CI: 1.01-1.06, P<0.001) indicated shorter DFS. Despite without statiscial significance, intratumoral M2 macrophage (OR 1.05, 95% CI: 0.99-1.10, P=0.081) was also associated with worse DFS. IRRS incorporating three intratumoral CD68-related markers and four intrastromal markers was constructed and validated to predict recurrence (high-risk group
Conclusions
UNASSIGNED
Our study suggested close interactions between CD68 and other immune markers in TME, demonstrating the prognostic value of CD68 in relapse prediction in resectable NSCLC.
Identifiants
pubmed: 35529784
doi: 10.21037/tlcr-21-916
pii: tlcr-11-04-523
pmc: PMC9073743
doi:
Types de publication
Journal Article
Langues
eng
Pagination
523-542Informations de copyright
2022 Translational Lung Cancer Research. All rights reserved.
Déclaration de conflit d'intérêts
Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-21-916/coif). WHL serves as an unpaid Associate Editors-in-Chief of Translational Lung Cancer Research. TY, HBZ, and YHC are employed by Genecast Biotechnology Co., Ltd. The other authors have no conflicts of interest to declare.
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