PT  - JOURNAL ARTICLE
AU  - Tolga Turan
AU  - Deepti Kannan
AU  - Maulik Patel
AU  - J. Matthew Barnes
AU  - Sonia G. Tanlimco
AU  - Rongze Lu
AU  - Kyle Halliwill
AU  - Sarah Kongpachith
AU  - Douglas E. Kline
AU  - Wouter Hendrickx
AU  - Alessandra Cesano
AU  - Lisa H. Butterfield
AU  - Howard L. Kaufman
AU  - Thomas J. Hudson
AU  - Davide Bedognetti
AU  - Francesco Marincola
AU  - Josue Samayoa
TI  - Immune oncology, immune responsiveness and the theory of everything
AID  - 10.1186/s40425-018-0355-5
DP  - 2018 Dec 01
TA  - Journal for ImmunoTherapy of Cancer
PG  - 50
VI  - 6
IP  - 1
4099  - http://jitc.bmj.com/content/6/1/50.short
4100  - http://jitc.bmj.com/content/6/1/50.full
SO  - J Immunother Cancer2018 Dec 01; 6
AB  - 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.Abbreviations:CIResCompensatory Immune ResistanceDCDendritic CellGEMGenetically Modified Mouse ModelsGEOGene Expression OmnibusGSKGlycogen synthase kinaseICRImmunologic Constant of RejectionIDOIndoleamine 2,3-dioxygenaseMAPKMitogen-activated protein kinasePI3KPhosphoinositide3-kinase-gammaPIResPrimary Immune ResistancePTPN2Protein tyrosine phosphatase non-receptor type 2SGKSerum and glucocorticoid kinasesResSignatures of ResistanceSTATSignal transducer and activator of transcription 1TCGAThe Cancer Genome AtlasTCIAThe Cancer Immunome AtlasTOCTwo-Option ChoiceTOETheory of Everything