The prognostic value of tumor-associated macrophages in leiomyosarcoma: a single institution study
Kristen N. Ganjoo,Daniela Witten,Manisha Patel,Inigo Espinosa,Trang H. La,Robert Tibshirani,Matt van de Rijn,Charlotte Jacobs,Robert B. West +8 more
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In this paper, the authors evaluated the outcome of patients with leiomyosarcoma (LMS) from a single institution according to the number of TAMs evaluated through 3 CSF1 associated proteins.Abstract:
INTRODUCTION High numbers of tumor-associated macrophages (TAMs) have been associated with poor outcome in several solid tumors. In 2 previous studies, we showed that colony stimulating factor-1 (CSF1) is secreted by leiomyosarcoma (LMS) and that the increase in macrophages and CSF1 associated proteins are markers for poor prognosis in both gynecologic and nongynecologic LMS in a multicentered study. The purpose of this study is to evaluate the outcome of patients with LMS from a single institution according to the number of TAMs evaluated through 3 CSF1 associated proteins. METHODS Patients with LMS treated at Stanford University with adequate archived tissue and clinical data were eligible for this retrospective study. Data from chart reviews included tumor site, size, grade, stage, treatment, and disease status at the time of last follow-up. The 3 CSF1 associated proteins (CD163, CD16, and cathepsin L) were evaluated by immunohistochemistry on tissue microarrays. Kaplan-Meier survival curves and univariate Cox proportional hazards models were fit to assess the association of clinical predictors as well as CSF1 associated proteins with overall survival. RESULTS A total of 52 patients diagnosed from 1983 to 2007 were evaluated. Univariate Cox proportional hazards models were fit to assess the significance of grade, size, stage, and the 3 CSF1 associated proteins in predicting OS. Grade, size, and stage were not significantly associated with survival in the full patient cohort, but grade and stage were significant predictors of survival in the gynecologic (GYN) LMS samples (P = 0.038 and P = 0.0164, respectively). Increased cathepsin L was associated with a worse outcome in GYN LMS (P = 0.049). Similar findings were seen with CD16 (P < 0.0001). In addition, CSF1 response enriched (all 3 stains positive) GYN LMS had a poor overall survival when compared with CSF1 response poor tumors (P = 0.001). These results were not seen in non-GYN LMS. CONCLUSIONS Our data form an independent confirmation of the prognostic significance of TAMs and the CSF1 associated proteins in LMS. More aggressive or targeted therapies could be considered in the subset of LMS patients that highly express these markers.read more
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Tumor-Infiltrating Dendritic Cells in Cancer Pathogenesis
TL;DR: Dendritic cells play a pivotal role in the tumor microenvironment, which is known to affect disease progression in many human malignancies, and promising developments in cancer-therapeutic strategies targeting tumor-infiltrating DCs to subdue their immunosuppressive functions and enhance their immune-stimulatory capacity are proposed.
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T-cell infiltration and clonality correlate with programmed cell death protein 1 and programmed death-ligand 1 expression in patients with soft tissue sarcomas.
Seth M. Pollack,Qianchuan He,Jennifer H. Yearley,Ryan O. Emerson,Marissa Vignali,Yuzheng Zhang,Mary W. Redman,Kelsey Baker,Sara Cooper,Bailey Donahue,Elizabeth T. Loggers,Lee D. Cranmer,Matthew B. Spraker,Y. David Seo,Venu G. Pillarisetty,Robert W. Ricciotti,Benjamin Hoch,Terrill K. McClanahan,Erin Murphy,Wendy M. Blumenschein,Steven M. Townson,Sharon Benzeno,Stanley R. Riddell,Robin L. Jones,Robin L. Jones +24 more
TL;DR: Patients with metastatic sarcomas have poor outcomes and although the disease may be amenable to immunotherapies, information regarding the immunologic profiles of soft tissue sarcoma (STS) subtypes is limited.
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Immunotherapy with single agent nivolumab for advanced leiomyosarcoma of the uterus: Results of a phase 2 study
Eytan Ben-Ami,Constance M. Barysauskas,Sarah Solomon,Kadija Tahlil,Rita Malley,Melissa Hohos,Kathleen Polson,Margaret Loucks,Mariano Severgnini,Tara Patel,Amy Cunningham,Scott J. Rodig,Scott J. Rodig,F. Stephen Hodi,Jeffrey A. Morgan,Priscilla Merriam,Andrew J. Wagner,Geoffrey I. Shapiro,Geoffrey I. Shapiro,Suzanne George +19 more
TL;DR: The goal of this study was to evaluate programmed‐death 1 (PD‐1) inhibition with nivolumab in this patient population of advanced uterine leiomyosarcoma.
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Tumor-associated macrophages and macrophage-related immune checkpoint expression in sarcomas
Amanda R. Dancsok,Dongxia Gao,Anna F. Lee,Sonja E. Steigen,Jean-Yves Blay,David Thomas,Robert G. Maki,Torsten O. Nielsen,Elizabeth G Demicco +8 more
TL;DR: Macrophage-focused immunomodulatory agents, such as CD47 or IDO-1 inhibitors, may be particularly worthwhile to pursue in sarcoma patients, alone or in combination with lymphocyte-focused agents.
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CD163 Is Required for Protumoral Activation of Macrophages in Human and Murine Sarcoma
Daisuke Shiraishi,Yukio Fujiwara,Hasita Horlad,Yoichi Saito,Toyohisa Iriki,Junko Tsuboki,Pan Cheng,Naomi Nakagata,Hiroshi Mizuta,Hirofumi Bekki,Yasuharu Nakashima,Yoshinao Oda,Motohiro Takeya,Yoshihiro Komohara +13 more
TL;DR: The results show that CD163 is involved in protumoral activation of macrophages and subsequent development and progression of tumors in mice and humans.
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