Dendritic Cell Cancer Therapy: Vaccinating the Right Patient at the Right Time

Abstract

Immune checkpoint inhibitors propelled the field of oncology with clinical responses in many different tumor types. Superior overall survival over chemotherapy has been reported in various metastatic cancers. Furthermore, prolonged disease-free and overall survival have been reported in the adjuvant treatment of stage III melanoma. Unfortunately, a substantial portion of patients do not obtain a durable response. Therefore, additional strategies for the treatment of cancer are still warranted. One of the numerous options is dendritic cell vaccination, which employs the central role of dendritic cells in activating the innate and adaptive immune system. Over the years, dendritic cell vaccination was shown to be able to induce an immunologic response, to increase the number of tumor infiltrating lymphocytes and to provide overall survival benefit for at least a selection of patients in phase II studies. However, with the success of immune checkpoint inhibition in several malignancies and considering the plethora of other treatment modalities being developed, it is of utmost importance to delineate the position of dendritic cell therapy in the treatment landscape of cancer. In this review, we address some key questions regarding the integration of dendritic cell vaccination in future cancer treatment paradigms.

Comprehensive analysis of DNA methylation and gene expression profiles in rectal cancer

“…In recent decades, there has been a revolution in the development of therapeutics aimed at harnessing the immune system to mount effective antitumor responses [52] . Tremendous progress has been made in the immunotherapy eld, such as engineered T-cell transfer, PD-1 blockade, and dendritic cell vaccination [53,54] . Our ndings may provide some clues for future immunotherapy research.…”

Immunotherapy in Multiple Myeloma

“…Vaccines have shown promising results in solid tumors, however their application in hematologic malignancies has been limited [205]. DCs are highly effective antigen presenting cells which have been extensively studied in the context of cancer vaccine therapy [206]. Physical fusion of DCs with myeloma cells (myeloma/DC fusion vaccine) was successfully employed in a phase 2 clinical trial where the vaccine was administered post-ASCT [207].…”

Resistance mechanisms in melanoma to immuneoncologic therapy with checkpoint inhibitors

“…Priming MHC class II receptors could potentially increase CD4+ T cell activity, bypassing difficulties seen with MHC I inhibition in melanoma cells with b-2 microglobulin and other mutations [238] . The addition of cancer vaccines (with either peptide vaccines or with primed dendritic cell vaccines) or the additional of radiation therapy to increase neoantigen formation and recognition may augment T cell responses and tumor recognition [35,[239][240][241][242] . Similarly, adding cytokines that stimulate the immune system such as IFN-a, IL-2, IL-12, IL-10 and the granulocyte-macrophage colony-stimulating factor (GM-CSF) to the treatment regimen or at high concentrations directly into the tumor microenvironment may also alter immune responses [243] .…”