TY - JOUR T1 - Peripheral immune-based biomarkers in cancer immunotherapy: can we realize their predictive potential? JF - Journal for ImmunoTherapy of Cancer JO - J Immunother Cancer DO - 10.1186/s40425-019-0799-2 VL - 7 IS - 1 SP - 325 AU - Andrew B. Nixon AU - Kurt A. Schalper AU - Ira Jacobs AU - Shobha Potluri AU - I-Ming Wang AU - Catherine Fleener Y1 - 2019/12/01 UR - http://jitc.bmj.com/content/7/1/325.abstract N2 - The immunologic landscape of the host and tumor play key roles in determining how patients will benefit from immunotherapy, and a better understanding of these factors could help inform how well a tumor responds to treatment. Recent advances in immunotherapy and in our understanding of the immune system have revolutionized the treatment landscape for many advanced cancers. Notably, the use of immune checkpoint inhibitors has demonstrated durable responses in various malignancies. However, the response to such treatments is variable and currently unpredictable, the availability of predictive biomarkers is limited, and a substantial proportion of patients do not respond to immune checkpoint therapy. Identification and investigation of potential biomarkers that may predict sensitivity to immunotherapy is an area of active research. It is envisaged that a deeper understanding of immunity will aid in harnessing the full potential of immunotherapy, and allow appropriate patients to receive the most appropriate treatments. In addition to the identification of new biomarkers, the platforms and assays required to accurately and reproducibly measure biomarkers play a key role in ensuring consistency of measurement both within and between patients. In this review we discuss the current knowledge in the area of peripheral immune-based biomarkers, drawing information from the results of recent clinical studies of a number of different immunotherapy modalities in the treatment of cancer, including checkpoint inhibitors, bispecific antibodies, chimeric antigen receptor T cells, and anti-cancer vaccines. We also discuss the various technologies and approaches used in detecting and measuring circulatory biomarkers and the ongoing need for harmonization.Abbreviations:AEAdverse eventALLAcute lymphoblastic leukemiaCARChimeric antigen receptorCDR3Complementarity-determining region 3CEACarcinoembryonic antigenCLLChronic lymphocytic leukemiaCMCentral memory (cell)EM1Effector-memory type 1 (cell)FDAFood and Drug AdministrationFLT3LGfms-related tyrosine kinase 3 ligandFNIHFoundation for the National Institutes of HealthICOSInducible co-stimulatorILInterleukinMDSCsMyeloid-derived suppressor cellsNCINational Cancer InstituteNCTNNational Clinical Trials NetworkNGSNext-generation sequencingNIHNational Institutes of HealthNKNatural killer (cell)NLRNeutrophil-to-lymphocyte ratioNSCLC Non-small cell lung carcinomaOSOverall survivalPACTPartnership for Accelerating Cancer TherapiesPBMCPeripheral blood mononuclear cellPD-1Programmed cell death protein 1PD-L1/2Programmed death ligand 1/2PFSProgression-free survivalRNA-seqRNA sequencingTCRT-cell receptorTEMRATerminally differentiated effector-memory T cellsTexExhausted-phenotype cd8 t (cell)TMBTumor mutational burdenTmemMemory t (cell)TregRegulatory T (cell)V-betaVariable-beta ER -