Cancer immunotherapy harnesses the patient's own immune system to specifically eliminate the tumor burden. The concept of cancer immunotherapy was first demonstrated by a surgeon, William Coley, in 1891. His work showed tumor regression in cancer patients treated with intratumoral inoculation of live, mixed bacterial extracts (1), suggesting that the immune response could be artificially augmented by the administration of immune adjuvant microbes, in this case, to eliminate malignant cells. Transformed cells harbor mutations that can be discriminated from self-antigens by T cells, a process known as cancer immunosurveillance. The mechanism underlying an effective antitumor response is divided into the following three phases (2):
Tumor-associated antigens are captured in situ or by ectopic delivery and processed by dendritic cells (DCs); Activated DCs undergo differentiation, maturation and homing to lymph nodes, where antigen loaded DC prime T cells; Antigen-specific T cells expand and enter the tumor microenvironment to eradicate the malignant cells. DCs, the most potent antigen presenting cells, are the key cellular element to induce the desired antitumor responses. Numerous cancer immunotherapy developments have focused on DCs because of their superior ability to bridge innate and adaptive immune responses. However, without an ideal adjuvant to deliver maturation signals to DCs, they will remain immature. Antigen presentation by DCs drives the production of Tregs, which maintain tolerance to self-antigens (3). Hence, to launch a robust antigen-specific antitumor response, an adjuvant is essential to activate DCs in the development of therapeutic cancer vaccines. A wide variety of immunostimulatory cytokines have been used in clinical studies. GM-CSF has been demonstrated to be a potent immune adjuvant that induces long-lasting antitumor immunity (4). GM-CSF belongs to the family of hematopoietic cytokines that promote the activation of myeloid cells such as DCs, macrophages and granulocytes (5). Growing evidence suggests that GM-CSF has adjuvant properties that promote DC activation and enhance tumor antigen presentation to T cells. In addition, the fact that bone marrow-derived DCs in a mouse model and monocyte-derived DCs from human peripheral blood mononuclear cells can be generated by GM-CSF and IL-4 in vitro has accelerated the study of DCs and their clinical applications. Cultured DCs pulsed with tumor-associated antigens (TAAs) can present peptides to MHC I to engage the T-cell receptor of CD8+ T cells for...
