Cancer therapeutic vaccines combined with immunotherapies and chemotherapies have garnered interest due to their potential synergistic effects[1]. Previous preclinical studies have demonstrated that DNA vaccines comprising melanoma antigen(s) fused to MIP3α delayed tumor growth, prolonged survival, and enhanced T-cell immunity in the B16F10 melanoma model[2–4]. MIP3α vaccine fusions have been shown to target antigen(s) to immature dendritic cells (iDC), with presentation through MHC class I and II[5, 6]. Here, antigens gp10025 − 235 and tyrosinase-related protein 2 (Trp2170 − 269) that have shown relevance in the clinic[7] are fused to MIP3α. When MIP3α-Gp100-Trp2 vaccine adjuvanted with delayed administration of CpG type C (henceforth referred to as “vaccine”) was combined with the drug treatments low-dose 5Aza-2’Deoxycytidine (5Aza) and a series of high and low doses of recombinant IFNα (IFN) (Fig. 1A), significantly greater anti-tumor activity was achieved, including increased dendritic cell (DC) and CD8 + T-cell infiltration into the tumor microenvironment (TME)[4, 8].
CD11c is a type I transmembrane protein forming part of the complement receptor 4 and has been shown to play a role in phagocytosis, cell migration, cytokine production, and T-cell proliferation[9]. CD11c binds to adhesion molecules, such as intercellular adhesion molecule 1 (ICAM1) and vascular cell adhesion molecule 1 (VCAM1), as well as the complement component 3 (C3) degradation product iC3b[10]. CD11c has been shown to be expressed on most DCs and some B cells, macrophages, and monocytes[11]. A subset of CD8 + T cells expressing CD11c + have been described in various tissues, infections, and cancers[9, 12–14] with the ability to become suppressor or effector cells[15–18].
The current study shows that CD8 + T cells expressing CD11c are enriched in the TME with combination treatment and correlated with tumor size in vaccinated groups, To our knowledge, this study is the first to show the presence of CD8 + CD11c + T cells in a tumor-associated antigen based therapeutic cancer vaccine system, and the data suggest that these cells are in higher numbers, are more robust, and are more potent with the combination treatments compared to vaccine alone or treatments alone. These cells are therefore likely to be critical components in the tumor suppression observed with the therapeutic regimen we have employed against the B16F10 melanoma.