Abstract
Despite significant advances in the field of cancer immunotherapy, the majority of patients still do not benefit from treatment and must rely on traditional therapies. Dendritic cells have long been a focus of cancer immunotherapy due to their role in inducing protective adaptive immunity, but cancer vaccines have shown limited efficacy in the past. With the advent of immune checkpoint blockade and the ability to identify patient-specific neoantigens, new vaccines, and combinatorial therapies are being evaluated in the clinic. Dendritic cells are also emerging as critical regulators of the immune response within tumors. Understanding how to augment the function of these intratumoral dendritic cells could offer new approaches to enhance immunotherapy, in addition to improving the cytotoxic and targeted therapies that are partially dependent upon a robust immune response for their efficacy. Here we will discuss the role of specific dendritic cell subsets in regulating the anti-tumor immune response, as well as the current status of dendritic cell-based immunotherapies, in order to provide an overview for future lines of research and clinical trials.
Highlights
Immunotherapy has revolutionized the treatment of many solid and hematological malignancies, with immune checkpoint blockade (ICB), adoptive cell therapy (ACT) using tumor infiltrating leukocytes (TIL), and vaccine strategies targeting different aspects of the immune-oncology cycle to improve the functionality of T lymphocytes
It was recently shown that for mice given adjuvant therapy with polyinosinic:polycytidilic acid (Poly [I:C]), monocyte DCs (moDCs) were required for the anti-tumor response, whereas cDC1 were dispensable [68]. moDCs have been shown to enhance the survival of adoptively transferred T cells [69] and may further regulate T cell activity within tumors through production of TNFα and NOS2 [18]
As dendritic cells (DCs), especially cDC1, tend to correlate with a positive prognosis when they are present in tumors, therapies targeting DCs focus on enhancing DC function, increasing their numbers, or bypassing the tumor microenvironment to promote systemic de novo antitumor immunity (Figure 2)
Summary
Reviewed by: Pooja Arora, Pfizer, United States Connie M. Specialty section: This article was submitted to Cancer Immunity and Immunotherapy, a section of the journal Frontiers in Immunology. Dendritic cells are emerging as critical regulators of the immune response within tumors. Understanding how to augment the function of these intratumoral dendritic cells could offer new approaches to enhance immunotherapy, in addition to improving the cytotoxic and targeted therapies that are partially dependent upon a robust immune response for their efficacy. We will discuss the role of specific dendritic cell subsets in regulating the anti-tumor immune response, as well as the current status of dendritic cell-based immunotherapies, in order to provide an overview for future lines of research and clinical trials
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