Dendritic cells (DCs) have received considerable attention as potential targets for the development of novel cancer immunotherapies. However, the clinical efficacy of DC-based vaccines remains suboptimal, largely reflecting local and systemic immunosuppression at baseline. An autologous DC-based vaccine (DCVAC) has recently been shown to improve progression-free survival and overall survival in randomized clinical trials enrolling patients with lung cancer (SLU01, NCT02470468) or ovarian carcinoma (SOV01, NCT02107937), but not metastatic castration-resistant prostate cancer (SP005, NCT02111577), despite a good safety profile across all cohorts. We performed biomolecular and cytofluorometric analyses on peripheral blood samples collected prior to immunotherapy from 1000 patients enrolled in these trials, with the objective of identifying immunological biomarkers that may improve the clinical management of DCVAC-treated patients. Gene signatures reflecting adaptive immunity and T cell activation were associated with favorable disease outcomes and responses to DCVAC in patients with prostate and lung cancer, but not ovarian carcinoma. By contrast, the clinical benefits of DCVAC were more pronounced among patients with ovarian carcinoma exhibiting reduced expression of T cell-associated genes, especially those linked to TH2-like signature and immunosuppressive regulatory T (TREG) cells. Clinical responses to DCVAC were accompanied by signs of antitumor immunity in the peripheral blood. Our findings suggest that circulating signatures of antitumor immunity may provide a useful tool for monitoring the potency of autologous DC-based immunotherapy.

Department of Gynaecology and Obstetrics Leuven Cancer Institute UZ Leuven Leuven Belgium

Department of Gynecology and Obstetrics 1st Faculty of Medicine Charles University University Hospital Bulovka Prague Czech Republic

Department of Gynecology and Obstetrics Charles University 3rd Faculty of Medicine and University Hospital Kralovske Vinohrady Prague Czech Republic

Department of Gynecology and Obstetrics Peking University 3rd Hospital Beijing Hebei Province China

Department of Immunology Charles University 2nd Faculty of Medicine and University Hospital Motol Prague Czech Republic

Department of Oncology Leuven Cancer Institute Laboratory of Gynaecologic Oncology KU Leuven Belgium

Department of Oncology Leuven Cancer Institute Laboratory of Tumor Immunology and Immunotherapy KU Leuven Belgium

Department of Pathology 3rd Faculty of Medicine And University Hospital Kralovske Vinohrady Prague Czech Republic

Department of Pediatric and Adult Rheumatology University Hospital Motol Prague Czech Republic

Gynecologic Oncology Center Department of Obstetrics and Gynecology 1st Faculty of Medicine Charles University and General University Hospital Prague Czech Republic

Laboratory of Cell Stress and Immunity Department of Cellular and Molecular Medicine KU Leuven Leuven Belgium

Sotio Biotech Prague Czech Republic

The Fingerland Department of Pathology Charles University Faculty of Medicine and University Hospital Hradec Kralove Czech Republic

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Trial watch: chemotherapy-induced immunogenic cell death in oncology

Mast Cells and Dendritic Cells as Cellular Immune Checkpoints in Immunotherapy of Solid Tumors

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ClinicalTrials.gov
NCT02470468, NCT02107937, NCT02111577