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23266066cir160037-sup-162291_2_supp_0_vvkjvj.pptx (1.95 MB)

Supplementary Figures 1 through 3 and Supplementary Tables 1 through 3 from Analyses of Pretherapy Peripheral Immunoscore and Response to Vaccine Therapy

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posted on 2023-04-03, 23:03 authored by Benedetto Farsaci, Renee N. Donahue, Italia Grenga, Lauren M. Lepone, Peter S. Kim, Brendan Dempsey, Janet C. Siebert, Nuhad K. Ibrahim, Ravi A. Madan, Christopher R. Heery, James L. Gulley, Jeffrey Schlom

Supplementary Figure S1: Gating strategy to identify classic peripheral immune cell types and refined immune cell subsets with phenotypes reflecting immune function that were used to generate the peripheral immunoscores of patients treated with docetaxel plus or minus PANVAC. Supplementary Figure S2: Gating strategy to identify classic peripheral immune cell types and refined immune cell subsets with phenotypes reflecting immune function that were used to generate the peripheral immunoscores of patients treated with Quadramet plus or minus PROSTVAC. Supplementary Figure S3: Point assignment method used in generating peripheral immunoscores. Supplementary Table S1: Antibodies and panels used in flow cytometry analysis to identify immune cells. Supplementary Table S2: PBMC frequencies (min, median, max) and bin cutoffs used in generating peripheral immunoscores in breast cancer patients treated with docetaxel +/- PANVAC vaccine and prostate cancer patients treated with Sm-153 (Quadramet) +/- PROSTVAC vaccine. Supplementary Table S3: Summation of points assigned to individual subsets to generate peripheral immunoscore.

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ARTICLE 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.