title: The Relationship of Immune Cell Signatures to Patient Survival Varies within and between Tumor Types.
abstract: Enhancing pre-existing anti-tumor immunity leads to therapeutic benefit for some patients, but why some tumors are more immunogenic than others remains unresolved. We took a unique systems approach to relate patient survival to immune gene expression in >3,500 tumor RNAseq profiles from a dozen tumor types. We found significant links between immune gene expression and patient survival in 8/12 tumor types, with tumors partitioned by gene expression comprising distinct molecular subtypes. T/NK cell genes were most clearly survival-related for melanoma, head and neck, and bladder tumors, whereas myeloid cell genes were most clearly survival-related with kidney and breast tumors. T/NK or myeloid cell gene expression was linked to poor prognosis in bladder and kidney tumors, respectively, suggesting tumor-specific immunosuppressive checkpoints. Our results suggest new biomarkers for existing cancer immunotherapies and identify targets for new immunotherapies.
authors.affiliation: Department of Systems Immunology, Benaroya Research Institute, 1201 Ninth Avenue, Seattle, WA 98101-2795, United States of America.
authors.forename: Peter S
authors.initials: PS
authors.lastname: Linsley
authors.affiliation: Department of Systems Immunology, Benaroya Research Institute, 1201 Ninth Avenue, Seattle, WA 98101-2795, United States of America.
authors.forename: Damien
authors.initials: D
authors.lastname: Chaussabel
authors.affiliation: Department of Systems Immunology, Benaroya Research Institute, 1201 Ninth Avenue, Seattle, WA 98101-2795, United States of America.
authors.forename: Cate
authors.initials: C
authors.lastname: Speake
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D007167:Immunotherapy; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D022423:Myeloid Cells / Q000276:immunology / Q000378:metabolism; D009369:Neoplasms / Q000276:immunology* / Q000401:mortality / Q000628:therapy; D011379:Prognosis; D012334:RNA, Neoplasm / Q000032:analysis / Q000378:metabolism; D016019:Survival Analysis; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D059467:Transcriptome; D051941:fms-Like Tyrosine Kinase 3 / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D012334:RNA, Neoplasm; C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3