Intratumoral dendritic cells in the anti-tumor immune response

Abstract

Immunotherapy has become a popular approach to the treatment of cancer and is well known in the clinical management of cancer because of the exciting recent results from immunotherapy targeting the costimulatory blockade.1 Another hot topic in this field is the combination of cancer immunotherapy and chemotherapy, and interestingly, T-cell immune response to the immunogenic cell death (ICD) induced by chemotherapeutic drugs is important to the therapeutic efficacy of certain types of chemotherapy. Therefore, the questions arising are what are the initiator and activator of the anti-tumor immune response in a tumor-bearing host receiving chemotherapy or combination therapy? Is there any possibility that effective antigen-presenting cells (APCs) exist in the immunosuppressive tumor microenvironment that process the tumor antigens released from the ICD of tumor cells and then initiate a tumor-specific T-cell response? Currently, it is well accepted that the tumor microenvironment, which consists of tumor cells, tumor-associated fibroblasts, vascular endothelial cells and immunosuppressive (or at least functionally impaired) immune cells, such as myeloid-derived suppressor cells, tumor-associated macrophages (TAMs), regulatory T cells and regulatory dendritic cells (DCs),2 is immunosuppressive and tumor-promoting. Thus, the current cancer immunotherapies mainly aim to reverse this tumor immunosuppression as well as trigger an effective anti-tumor immune response, enhancing the cytotoxic ability of T cells to reject tumors.3 Therefore, further identification of the immune cell types in the tumor microenvironment, with immune-tolerating or immune-activating potential, will provide new opportunities for the design of cancer immunotherapeutics. More recently, intratumoral CD103+ DCs have been identified as active APCs in the tumor microenvironment that process antigens and are crucial to the induction of an anti-tumoral T-cell response,4,5 thus challenging the concept that immune cells are all immunosuppressive or functionally impaired in the tumor microenvironment. These new findings will inspire immunologists to rethink the interactions between the host immune system and tumors and develop new approaches to cancer immunotherapy.