Rebounding of dendritic cells post chemotherapy: Implication for cancer immunotherapy

Immunology and Biotechnology Unit, Zoology Department, Faculty of Science, Tanta University, Egypt Th e success of anti-tumor immunity depends on the generation of functionally eff ective T cells. Adoptive cell therapy (ACT) of autologous tumor-reactive T cells aft er chemotherapy a nd followed by vaccination is a promising approach for generation of functional T cells for cancer immunotherapy. Th is ACT modality consists of in vitro stimulation of T cells from a host own peripheral blood or tumor and then infusing them back to the same host blood followed by vaccination regimen such as peptide or peptide-pulsed dendritic cells (DCs). Th e host is irradiated or treated with chemotherapeutic drug such as cyclophosphamide (CTX) prior ACT to induce lymphopenia. Th e cellular and molecular mechanisms underlying the benefi cial eff ects of lymphodepletion in the context of adoptive T cell therapy and vaccination, however, are not well understood. Defi ning these mechanisms would signifi cantly improve the application of lymphodepletion to ACT. Our recent studies have identifi ed expansion of DCs, the central player of immune response, as a potential mechanism. We have utilized the toll-like receptor 3 (TLR3) agonist poly(I:C), a synthetic viral mimic double-stranded RNA, to induce the full activation of DCs expanded in vivo aft er chemotherapy and during vaccination with defi ned tumor antigens, resulting in effi cacious therapeutic anti-tumor responses. Our results reveal that the combination of T cell therapy and vaccination in the presence of a potent adjuvant such as a TLR agonist at precise timing post chemotherapy opens a new avenue for cancer immunotherapy that can be translated into the clinical setting to cure diff erent cancers.