PT  - JOURNAL ARTICLE
AU  - Mushtaq, Muhammad Umair
AU  - Papadas, Athanasios
AU  - Pagenkopf, Adam
AU  - Flietner, Evan
AU  - Morrow, Zachary
AU  - Chaudhary, Sibgha Gull
AU  - Asimakopoulos, Fotis
TI  - Tumor matrix remodeling and novel immunotherapies: the promise of matrix-derived immune biomarkers
AID  - 10.1186/s40425-018-0376-0
DP  - 2018 Dec 01
TA  - Journal for ImmunoTherapy of Cancer
PG  - 65
VI  - 6
IP  - 1
4099  - http://jitc.bmj.com/content/6/1/65.short
4100  - http://jitc.bmj.com/content/6/1/65.full
SO  - J Immunother Cancer2018 Dec 01; 6
AB  - Recent advances in our understanding of the dynamics of cellular cross-talk have highlighted the significance of host-versus-tumor effect that can be harnessed with immune therapies. Tumors exploit immune checkpoints to evade adaptive immune responses. Cancer immunotherapy has witnessed a revolution in the past decade with the development of immune checkpoint inhibitors (ICIs), monoclonal antibodies against cytotoxic T lymphocyte antigen 4 (CTLA-4) and programmed cell death protein 1 (PD-1) or their ligands, such as PD1 ligand 1 (PD-L1). ICIs have been reported to have activity against a broad range of tumor types, in both solid organ and hematologic malignancy contexts. However, less than one-third of the patients achieve a durable and meaningful treatment response. Expression of immune checkpoint ligands (e.g., PD-L1), mutational burden and tumor-infiltrating lymphocytes are currently used as biomarkers for predicting response to ICIs. However, they do not reliably predict which patients will benefit from these therapies. There is dire need to discover novel biomarkers to predict treatment efficacy and to identify areas for development of combination strategies to improve response rates. Emerging evidence suggests key roles of tumor extracellular matrix (ECM) components and their proteolytic remodeling products in regulating each step of the cancer-immunity cycle. Here we review tumor matrix dynamics and matrix remodeling in context of anti-tumor immune responses and immunotherapy and propose the exploration of matrix-based biomarkers to identify candidates for immune therapy.Abbreviations:ADAMAdamalysins, including A disintegrin and metalloproteinasesADAMTSA disintegrin and metalloproteinase with thrombospondin motifsCARChimeric antigen receptorCLEVER-1Common lymphatic endothelial and vascular endothelial receptor 1CTLCytotoxic lymphocytes (CD8+)CTLA-4Cytotoxic T lymphocyte antigen 4CAFsCancer-associated fibroblastscDCsClassical dendritic cellsDCsDendritic cellsECMExtracellular matrixEMTEpithelial-to-mesenchymal transitionFAPFibroblast activation proteinFGFFibroblast growth factorsFcγRsFc-gamma receptorsFDAFood and Drug AdministrationFOXP3Forkhead-box P3GPIGlycosylphosphatidylinisotolHAHyaluronanHSPGsHeparin sulfate proteoglycansICIImmune checkpoint inhibitorICAMIntercellular cell adhesion moleculesIFNInterferonsILInterleukinsIL2RαInterleukin-2 receptor chair-alphaLAIR-1Leukocyte Associated Ig-like Receptor-1MMPsMatrix metalloproteinasesMSCsMesenchymal stem cellsmAbMonoclonal antibodiesMSIMicrosatellite instabilityMSSMicrosatellite-stableMDSCsMyeloid-derived-suppressor cellsNSCLCNon-small cell lung cancerpDCsPlasmacytoid dendritic cellsPDGF-βPlatelet-derived growth factor-βPD-1Programmed cell death protein 1PD-L1Programmed cell death protein ligand 1PD-L2Programmed cell death protein ligand 2SLRPsSmall leucine-rich proteoglycansTregsRegulatory T cells (CD4+)TIMPsTissue inhibitors of metalloproteinasesTNFαtumor necrosis factor-alphaTCRT cell receptorTLRToll-like receptorTGF-βTransforming growth factor-betaTMETumor microenvironmentTAMsTumor-associated macrophagesTANsTumor-associated neutrophilsVCAMVascular cell adhesion moleculesVCANVersicanVEGFVascular endothelial growth factorVLA-4Very Late Antigen-4