CD4+ T cell and M2 macrophage infiltration predict dedifferentiated liposarcoma patient outcomes.
Date
2021-08-01ICR Author
Author
Schroeder, BA
LaFranzo, NA
LaFleur, BJ
Gittelman, RM
Vignali, M
Zhang, S
Flanagan, KC
Rytlewski, J
Riolobos, L
Schulte, BC
Kim, TS
Chen, E
Smythe, KS
Wagner, MJ
Mantilla, JG
Campbell, JS
Pierce, RH
Jones, RL
Cranmer, LD
Pollack, SM
Type
Journal Article
Metadata
Show full item recordAbstract
BACKGROUND: Dedifferentiated liposarcoma (DDLPS) is one of the most common soft tissue sarcoma subtypes and is devastating in the advanced/metastatic stage. Despite the observation of clinical responses to PD-1 inhibitors, little is known about the immune microenvironment in relation to patient prognosis. METHODS: We performed a retrospective study of 61 patients with DDLPS. We completed deep sequencing of the T-cell receptor (TCR) β-chain and RNA sequencing for predictive modeling, evaluating both immune markers and tumor escape genes. Hierarchical clustering and recursive partitioning were employed to elucidate relationships of cellular infiltrates within the tumor microenvironment, while an immune score for single markers was created as a predictive tool. RESULTS: Although many DDLPS samples had low TCR clonality, high TCR clonality combined with low T-cell fraction predicted lower 3-year overall survival (p=0.05). Higher levels of CD14+ monocytes (p=0.02) inversely correlated with 3-year recurrence-free survival (RFS), while CD4+ T-cell infiltration (p=0.05) was associated with a higher RFS. Genes associated with longer RFS included PD-1 (p=0.003), ICOS (p=0.006), BTLA (p=0.033), and CTLA4 (p=0.02). In a composite immune score, CD4+ T cells had the strongest positive predictive value, while CD14+ monocytes and M2 macrophages had the strongest negative predictive values. CONCLUSIONS: Immune cell infiltration predicts clinical outcome in DDLPS, with CD4+ cells associated with better outcomes; CD14+ cells and M2 macrophages are associated with worse outcomes. Future checkpoint inhibitor studies in DDLPS should incorporate immunosequencing and gene expression profiling techniques that can generate immune landscape profiles.
Collections
Subject
CD4-positive T-lymphocytes
immunity
macrophages
sarcoma
tumor microenvironment
Adolescent
Adult
Aged
Aged, 80 and over
CD4-Positive T-Lymphocytes
Cell Differentiation
Child
Child, Preschool
Female
Humans
Infant
Infant, Newborn
Liposarcoma
Macrophages
Male
Middle Aged
Patient Outcome Assessment
Retrospective Studies
Young Adult
Language
eng
Date accepted
2021-07-26
License start date
2021-08-01
Citation
Journal for ImmunoTherapy of Cancer, 2021, 9 (8), pp. e002812 -
Publisher
BMJ PUBLISHING GROUP