Tumor growth is controlled by natural antitumor immune responses alone or by augmented immune reactivity resulting from different forms of immunotherapy, which has demonstrated clinical benefit in numerous studies, although the overall percentage of patients with durable clinical responses remains limited. This is attributed to the heterogeneity of the disease, the inclusion of late-stage patients with no other treatment options and advanced tumor-associated immunosuppression, which may be consolidated by certain types of chemotherapy. Despite variable responsiveness to distinct types of immunotherapy, therapeutic cancer vaccination has shown meaningful efficacy for a variety of cancers. A key step during cancer vaccination involves the appropriate modeling of the functional state of dendritic cells (DCs) capable of co-delivering four critical signals for proper instruction of tumor antigen-specific T cells. However, the education of DCs, either directly in situ, or ex vivo by various complex procedures, lacks standardization. Also, it is questioned whether ex vivo-prepared DC vaccines are superior to in situ-administered adjuvant-guided vaccines, although both approaches have shown success. Evaluation of these variables is further complicated by a lack of consensus in evaluating vaccination clinical study end points. We discuss the role of signals needed for the preparation of classic in situ and modern ex vivo DC vaccines capable of proper reprogramming of antitumor immune responses in patients with cancer.

Advanced Cell Immunotherapy Unit Department of Pharmacology Medical Faculty Masaryk University Brno Czech Republic; Cellthera Ltd Brno Czech Republic

Department of Immunology Center of Oncosurgery Institute of Oncology Vilnius University Vilnius Lithuania

Epitopoietic Research Corporation Namur Belgium; Department of Neurosurgery Les Cliniques du Sud Luxembourg Arlon Belgium

Immune Intervention Cell Biology and Immunology Group Wageningen University Wageningen The Netherlands; Epitopoietic Research Corporation Namur Belgium

INSERM U970 PARCC Université Paris Descartes Paris France; Service d'Immunologie Biologique Hopital Européen Georges Pompidou Paris France

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