title: Analyses of Pretherapy Peripheral Immunoscore and Response to Vaccine Therapy.
abstract: Tumor immunoscore analyses, especially for primary colorectal cancer and melanoma lesions, provide valuable prognostic information. Metastatic lesions of many carcinoma types, however, are often not easily accessible. We hypothesized that immune cells in peripheral blood may differ among individual patients with metastatic disease, which, in turn, may influence their response to immunotherapy. We thus analyzed immune cell subsets within peripheral blood mononuclear cells to determine if a "peripheral immunoscore" could have any prognostic significance for patients before receiving immunotherapy. Patients with metastatic breast cancer were randomly assigned to receive docetaxel ± PANVAC vaccine. In another trial, prostate cancer patients with metastatic bone lesions were randomly assigned to receive a bone-seeking radionuclide ± PROSTVAC vaccine. Predefined analyses of "classic" immune cell types (CD4, CD8, natural killer cells, regulatory T cells, myeloid-derived suppressor cells, and ratios) revealed no differences in progression-free survival (PFS) for either arm in both trials. Predefined analyses of refined immune cell subsets for which a biologic function had been previously reported also showed no significant prognostic value in PFS for patients receiving either docetaxel or radionuclide alone; however, in patients receiving these agents in combination with vaccine, the peripheral immunoscore of refined subsets revealed statistically significant differences in PFS (P < 0.001) for breast cancer patients receiving docetaxel plus vaccine, and in prostate cancer patients receiving radionuclide plus vaccine (P = 0.004). Larger randomized studies will be required to validate these findings. These studies, however, provide the rationale for the evaluation of refined immune cell subsets to help determine which patients may benefit most from immunotherapy. Cancer Immunol Res; 4(9); 755-65. ©2016 AACR.
authors.affiliation: Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland.
authors.forename: Benedetto
authors.initials: B
authors.lastname: Farsaci
authors.affiliation: Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland.
authors.forename: Renee N
authors.initials: RN
authors.lastname: Donahue
authors.affiliation: Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland.
authors.forename: Italia
authors.initials: I
authors.lastname: Grenga
authors.affiliation: Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland.
authors.forename: Lauren M
authors.initials: LM
authors.lastname: Lepone
authors.affiliation: Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland.
authors.forename: Peter S
authors.initials: PS
authors.lastname: Kim
authors.affiliation: Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland.
authors.forename: Brendan
authors.initials: B
authors.lastname: Dempsey
authors.affiliation: CytoAnalytics, Denver, Colorado.
authors.forename: Janet C
authors.initials: JC
authors.lastname: Siebert
authors.affiliation: Department of Breast Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Nuhad K
authors.initials: NK
authors.lastname: Ibrahim
authors.affiliation: Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Ravi A
authors.initials: RA
authors.lastname: Madan
authors.affiliation: Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland.
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Heery
authors.affiliation: Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: James L
authors.initials: JL
authors.lastname: Gulley
authors.affiliation: Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland. js141c@nih.gov.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Schlom
mesh_terms: D015415:Biomarkers; D019496:Cancer Vaccines / Q000276:immunology* / Q000627:therapeutic use*; D016000:Cluster Analysis; D003131:Combined Modality Therapy; D020869:Gene Expression Profiling; D006801:Humans; D007109:Immunity; D007167:Immunotherapy; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D009369:Neoplasms / Q000276:immunology* / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D019496:Cancer Vaccines