RT Journal Article SR Electronic T1 Metastatic breast cancers have reduced immune cell recruitment but harbor increased macrophages relative to their matched primary tumors JF Journal for ImmunoTherapy of Cancer JO J Immunother Cancer FD BMJ Publishing Group Ltd SP 265 DO 10.1186/s40425-019-0755-1 VO 7 IS 1 A1 Zhu, Li A1 Narloch, Jessica L. A1 Onkar, Sayali A1 Joy, Marion A1 Broadwater, Gloria A1 Luedke, Catherine A1 Hall, Allison A1 Kim, Rim A1 Pogue-Geile, Katherine A1 Sammons, Sarah A1 Nayyar, Naema A1 Chukwueke, Ugonma A1 Brastianos, Priscilla K. A1 Anders, Carey K. A1 Soloff, Adam C. A1 Vignali, Dario A. A. A1 Tseng, George C. A1 Emens, Leisha A. A1 Lucas, Peter C. A1 Blackwell, Kimberly L. A1 Oesterreich, Steffi A1 Lee, Adrian V. YR 2019 UL http://jitc.bmj.com/content/7/1/265.abstract AB The interplay between the immune system and tumor progression is well recognized. However, current human breast cancer immunophenotyping studies are mostly focused on primary tumors with metastatic breast cancer lesions remaining largely understudied. To address this gap, we examined exome-capture RNA sequencing data from 50 primary breast tumors (PBTs) and their patient-matched metastatic tumors (METs) in brain, ovary, bone and gastrointestinal tract. We used gene expression signatures as surrogates for tumor infiltrating lymphocytes (TILs) and compared TIL patterns in PBTs and METs. Enrichment analysis and deconvolution methods both revealed that METs had a significantly lower abundance of total immune cells, including CD8+ T cells, regulatory T cells and dendritic cells. An exception was M2-like macrophages, which were significantly higher in METs across the organ sites examined. Multiplex immunohistochemistry results were consistent with data from the in-silico analysis and showed increased macrophages in METs. We confirmed the finding of a significant reduction in immune cells in brain METs (BRMs) by pathologic assessment of TILs in a set of 49 patient-matched pairs of PBT/BRMs. These findings indicate that METs have an overall lower infiltration of immune cells relative to their matched PBTs, possibly due to immune escape. RNAseq analysis suggests that the relative levels of M2-like macrophages are increased in METs, and their potential role in promoting breast cancer metastasis warrants further study.Li Zhu, Jessica L. Narloch and Sayali Onkar are Co-first authors.Abbreviations:BOMMetastatic breast tumor in boneBRMMetastatic breast tumor in brainDEDifferential expressionecRNA-seqExome-capture RNA sequencingFFPEFormalin fixed paraffin embeddedGIGastrointestinal tractGIMMetastatic breast tumor in gastrointestinal tractGSVAGene set variation analysisGTExGenotype-Tissue ExpressionH&EHematoxylin & EosinHRHormone receptorMETMetastatic breast tumorMFSMetastasis-free-survivalmIFMultiplexed immunofluorescenceOVMMetastatic breast tumor in ovaryPBTPrimary breast tumorSPMSurvival-post-metastasisssGSEASingle-sample gene set enrichment analysissTILStromal tumor infiltrating lymphocyteTILTumor infiltrating lymphocytesTMETumor microenvironmentTNBCTriple negative breast cancer