Ongoing research in order to broaden the impact of these therapeutics. The validation of biomarkers predictive of treatment outcomes is paramount to identifying the patients who are most likely to benefit from treatment and/or to provide an early indication of therapy response (a topic* Correspondence: [email protected] 1 Department of Transfusion Medicine, National Institutes of Health, 10 Center Drive, Building 10, Room 3C720, Bethesda, MD 20892, USA Full list of author information is available at the end of the articleaddressed by WG1). At present no definitive biomarkers have been identified that can be used to predict which patients are most likely to have a clinical benefit. In melanoma, several preliminary biomarkers have been investigated in response to ipilimumab (anti-CTLA-4) treatment, but none have been validated in subsequent studies [2?]. GGTI298 web peripheral blood is a readily (and repeatedly) accessible compartment that can yield valuable prognostic information, but the relationship between local immune responses within the tumor microenvironment (TME) and the peripheral immune system remains incompletely understood. Emerging data show that cancer and immune cells may be phenotypically and functionally different between primary tumors and metastatic tissues [6, 7]. Thus, it is often essential to monitor additional tissues to understand the impact of different immunotherapies on the host immune response. For example, tumor draining lymph nodes (TDLN) represent both a metastatic site as well as a major site of cancer-immune?The Author(s). 2017 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Stroncek et al. Journal for PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/26080418 ImmunoTherapy of Cancer (2017) 5:Page 2 ofinteractions [8, 9], the bone marrow is the dominant site of tumor involvement in several hematologic malignancies, and the cross-talk between the host and the commensal microbiome regulates many physiological functions including inflammation and immunity [10?2]. In addition, for adoptive cell therapies, it is important to analyze the administered cells as well as their persistence and trafficking in vivo. It is critical to develop systematic approaches to monitor immune responses and to interpret the data obtained as the number of compartments and potential biomarkers analyzed increases. Biologic samples can now be analyzed at the cellular, DNA, transcriptional, epigenetic, post-transcriptional and protein levels, and the analysis of multiple compartments at several levels yields massive quantities of data, which require the use of novel analytic bioinformatics methods. The purpose of this review is to describe systematic approaches to monitor immune responses to cancer immunotherapy. Using blood, the TME, microbiome, bone marrow (BM) and transferred T cells as examples, the nature and timing of the samples that should be collected will be discussed as well as the potential types of measures, assays, and analyses. In particular, the unique collec.