Immune oncology, immune responsiveness and the theory of everything

Anti-cancer immunotherapy is encountering its own checkpoint. Responses are dramatic and long lasting but occur in a subset of tumors and are largely dependent upon the pre-existing immune contexture of individual cancers. Available data suggest that three landscapes best define the cancer microenvi...

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Published inJournal for immunotherapy of cancer Vol. 6; no. 1; p. 50
Main Authors Turan, Tolga, Kannan, Deepti, Patel, Maulik, Matthew Barnes, J, Tanlimco, Sonia G, Lu, Rongze, Halliwill, Kyle, Kongpachith, Sarah, Kline, Douglas E, Hendrickx, Wouter, Cesano, Alessandra, Butterfield, Lisa H, Kaufman, Howard L, Hudson, Thomas J, Bedognetti, Davide, Marincola, Francesco, Samayoa, Josue
Format Journal Article
LanguageEnglish
Published England BioMed Central Ltd 05.06.2018
BMJ Publishing Group LTD
BioMed Central
BMJ Publishing Group
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Summary:Anti-cancer immunotherapy is encountering its own checkpoint. Responses are dramatic and long lasting but occur in a subset of tumors and are largely dependent upon the pre-existing immune contexture of individual cancers. Available data suggest that three landscapes best define the cancer microenvironment: immune-active, immune-deserted and immune-excluded. This trichotomy is observable across most solid tumors (although the frequency of each landscape varies depending on tumor tissue of origin) and is associated with cancer prognosis and response to checkpoint inhibitor therapy (CIT). Various gene signatures (e.g. Immunological Constant of Rejection - ICR and Tumor Inflammation Signature - TIS) that delineate these landscapes have been described by different groups. In an effort to explain the mechanisms of cancer immune responsiveness or resistance to CIT, several models have been proposed that are loosely associated with the three landscapes. Here, we propose a strategy to integrate compelling data from various paradigms into a "Theory of Everything". Founded upon this unified theory, we also propose the creation of a task force led by the Society for Immunotherapy of Cancer (SITC) aimed at systematically addressing salient questions relevant to cancer immune responsiveness and immune evasion. This multidisciplinary effort will encompass aspects of genetics, tumor cell biology, and immunology that are pertinent to the understanding of this multifaceted problem.
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ISSN:2051-1426
2051-1426
DOI:10.1186/s40425-018-0355-5