Decoding immunogenic cell death from a dendritic cell perspective

Abstract

SummaryDendritic cells (DCs) are myeloid cells bridging the innate and adaptive immune system. By cross‐presenting tumor‐associated antigens (TAAs) liberated upon spontaneous or therapy‐induced tumor cell death to T cells, DCs occupy a pivotal position in the cancer immunity cycle. Over the last decades, the mechanisms linking cancer cell death to DC maturation, have been the focus of intense research. Growing evidence supports the concept that the mere transfer of TAAs during the process of cell death is insufficient to drive immunogenic DC maturation unless this process is coupled with the release of immunomodulatory signals by dying cancer cells. Malignant cells succumbing to a regulated cell death variant called immunogenic cell death (ICD), foster a proficient interface with DCs, enabling their immunogenic maturation and engagement of adaptive immunity against cancer. This property relies on the ability of ICD to exhibit pathogen‐mimicry hallmarks and orchestrate the emission of a spectrum of constitutively present or de novo‐induced danger signals, collectively known as damage‐associated molecular patterns (DAMPs). In this review, we discuss how DCs perceive and decode danger signals emanating from malignant cells undergoing ICD and provide an outlook of the major signaling and functional consequences of this interaction for DCs and antitumor immunity.

Synergistic action of gemcitabine and celecoxib in promoting the antitumor efficacy of anti-programmed death-1 monoclonal antibody by triggering immunogenic cell death

“…Previous studies found that more severe ER stress can lead to higher ICD ( 25 , 26 ). Direct ROS-based ER stress is more effective for induction of ICD than is secondary collateral ER stress.…”

Ferroptosis Amplifier Remodels Redox Homeostasis for Enhanced Cancer Chemoimmunotherapy

“…Immunotherapy, especially immune checkpoint blockade (ICB), has been a breakthrough in cancer treatment in recent years. − However, its clinical efficacy is often limited by T-cell deprivation and poor immunogenicity in solid tumors. − Many efforts have been made to turn “immune-cold” to “immune-hot” tumors to potentiate immunotherapy. , Among them, chemotherapy can induce immunogenic cell death (ICD) to reinforce tumor immunogenicity while killing tumor cells, thus showing great potential to synergize with ICB . During ICD, the dying tumor cells can release damage-associated molecular patterns (DAMPs) to stimulate dendritic cells (DCs) maturation and further facilitate effector T-cell infiltration. − However, the high expression of redox substances in the tumor microenvironment (TME) causes abnormal redox homeostasis, which restricts the chemotherapy-induced ICD effect . Thus, destroying redox homeostasis in the TME is necessary for amplifying chemotherapy-sensitized ICB therapy.…”