Document Type : Review Article


1 Department of Immunology, Dezful University of Medical Sciences, Dezful, Iran

2 Ontario Cancer Institute, University Health Network, Toronto, Ontario, Canada

3 Department of Immunology, Medical School, Kerman University of Medical Sciences, Kerman

4 Cancer Research Center, Department of Immunology, Semnan University of Medical Sciences, Semnan, Iran

5 Immune and Gene Therapy Laboratory, Department of Oncology-Pathology, Karolinska Cancer Center, Karolinska University Hospital, Solna and Karolinska Institute, Stockholm, Sweden

6 Department of Immunology, School of Medicine, Bushehr University of Medical Sciences, Bushehr, Iran


Cancer immunotherapy (passive or active) involves treatments which promote the ability of the immune system to fight tumor cells. Several types of immunotherapeutic agents, such as monoclonal antibodies, immune checkpoint inhibitors, non-specific immunomodulatory agents, and cancer vaccines are currently under intensive investigation in preclinical and clinical trials. Cancer vaccines induce permanent activation of the immune system and may be considered the most promising method for cancer treatment, especially in combination with other agents of passive immunotherapy. Among various approaches to cancer vaccines, whole tumor cell vaccines have been attracting attention for several years. Despite their low to moderate clinical effects, these vaccines have numerous advantages. Their ability to generate immune responses against tumor-associated antigens reduces the possibility for tumor cells to escape and facilitates the development of “off-the-shelf” allogeneic tumor vaccines. Understanding the reciprocal interactions between tumor cells and leukocytes is a key to harness the full potential of whole cell vaccination. Cytokines are considered as potent immunomodulatory molecules which behave as adjuvants in whole tumor cell vaccines. Improved mechanistic understanding of key cytokines in tumor immunity will serve as a resource for rational design of whole cell cancer vaccines. Although there are several reports about the use of different immunostimulatory cytokines as adjuvants, interleukin (IL)-12 appears to have superior effects compared to other cytokines. This review describes the effects of IL-12 compared to other immunomodulatory cytokines, such as IL-2 and IL-15, and highlights its application in whole cell tumor vaccination.