Combination of all-trans retinoic acid and a human papillomavirus therapeutic vaccine suppresses the number and function of immature myeloid cells and enhances antitumor immunity

Despite advances in the development of human papillomavirus (HPV) prophylactic vaccines, little progress has been made in the field of therapeutic vaccines in recent years. In the present study, we found a significant accumulation of immature myeloid cells (ImC) in large TC-1 tumors and demonstrated that a HPV therapeutic vaccine restored antitumor immune responses with the correction of aberrant myeloid cell differentiation by all-trans retinoic acid (ATRA). Our study demonstrated that combining ATRA with vaccination not only decreased the number of Gr-1⁺ CD11b⁺ ImC, but for the first time also suppressed the function of Gr-1⁺ CD11b⁺ ImC with decreased expression of CD80. Furthermore, large numbers of CD11c⁺ CD80⁺, CD11c⁺ CD86⁺;, and CD11c⁺ MHCII⁺ mature dendritic cells were recruited. The combination therapy generated significantly increased numbers of functional E7-specific T cells with elevated interferon-γ secretion and enhanced cytotoxic T-cell activity. These findings suggest potential clinical benefits for the combined use of ATRA and HPV therapeutic vaccines.