@article{5a78af1fd5124e86978561ee08ca5ad8,
title = "CD4+ T cell and M2 macrophage infiltration predict dedifferentiated liposarcoma patient outcomes",
abstract = "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.",
keywords = "CD4-positive T-lymphocytes, immunity, macrophages, sarcoma, tumor microenvironment",
author = "Schroeder, {Brett A.} and Lafranzo, {Natalie A.} and Lafleur, {Bonnie J.} and Gittelman, {Rachel M.} and Marissa Vignali and Shihong Zhang and Flanagan, {Kevin C.} and Julie Rytlewski and Laura Riolobos and Schulte, {Brian C.} and Kim, {Teresa S.} and Eleanor Chen and Smythe, {Kimberly S.} and Wagner, {Michael J.} and Mantilla, {Jose G.} and Campbell, {Jean S.} and Pierce, {Robert H.} and Jones, {Robin L.} and Cranmer, {Lee D.} and Pollack, {Seth M.}",
note = "Funding Information: Competing interests BAS, SZ, LRS, BCS, KSS, JGM, EC, JSC, and RHP declare no potential conflicts of interest. SMP reported research funding from Merck during the conduct of the study; research funding from EMD Serono, Incyte, Presage, Janssen, OncoSec, and Juno and consulting, honoraria, and advisory activity with GlaxoSmithKline, Eli Lilly and Company, Seattle Genetics, Bayer, Tempus, Daiichi Sankyo, and Blueprint Medicine, outside the submitted work. NAL and KCF are employed by Cofactor Genomics, Inc, the company that developed and produces the ImmunoPrism{\textregistered} reagent kit and informatics tools used in this article. BJL is a paid consultant for Cofactor Genomics, Inc. RMG and MV have a financial interest in Adaptive Biotechnologies. JR has equity in Adaptive Biotechnologies, equity and employment with Bristol Myers Squibb. MJW reported research funding from Athenex, Deciphera, Incyte, Tempus, Adaptimmune, and GlaxoSmithKline and consulting, honoraria, and advisory activity with Tempus, Deciphera, and Adaptimmune, outside the submitted work. RLJ reported grants from Merck during the conduct of the study; research support from Merck Sharp & Dohme and GlaxoSmithKline and consultation fees from Adaptimmune, Athenex, Blueprint Medicine, Clinigen, Eisai, Epizyme, Daiichi Sankyo, Deciphera, Immune Design, Eli Lilly and Company, Merck, Pharma Mar, and UpToDate, outside the submitted work; in addition, RLJ had a patent to biomarker, issued. LDC receives research funding, paid to institution, from Eli Lilly, AADi, BluePrint Medicine, Iterion, Gradalis, Philogen, Advenchen Laboratories, and CBA Pharma. LDC institution has received funding from Eli Lilly for conduct of clinical trials. LDC has received honoraria or has served on advisory boards for BluePrint Medicines and Regeneron. Funding Information: Funding Funding for this study was provided by CA180380 and the Sarcoma Foundation of America. SMP was also supported by R01CA244872, CA180380, a grant from the V Foundation, and the Seattle Translational Tumor Research (STTR). Publisher Copyright: {\textcopyright} 2021 BMJ Publishing Group. All rights reserved.",
year = "2021",
month = aug,
day = "31",
doi = "10.1136/jitc-2021-002812",
language = "English (US)",
volume = "9",
journal = "Journal for ImmunoTherapy of Cancer",
issn = "2051-1426",
publisher = "BioMed Central",
number = "8",
}