Immunogenic Cell Death Activates the Tumor Immune Microenvironment to Boost the Immunotherapy Efficiency

Abstract

Tumor immunotherapy is only effective in a fraction of patients due to a low response rate and severe side effects, and these challenges of immunotherapy in clinics can be addressed through induction of immunogenic cell death (ICD). ICD is elicited from many antitumor therapies to release danger associated molecular patterns (DAMPs) and tumor‐associated antigens to facilitate maturation of dendritic cells (DCs) and infiltration of cytotoxic T lymphocytes (CTLs). The process can reverse the tumor immunosuppressive microenvironment to improve the sensitivity of immunotherapy. Nanostructure‐based drug delivery systems (NDDSs) are explored to induce ICD by incorporating therapeutic molecules for chemotherapy, photosensitizers (PSs) for photodynamic therapy (PDT), photothermal conversion agents for photothermal therapy (PTT), and radiosensitizers for radiotherapy (RT). These NDDSs can release loaded agents at a right dose in the right place at the right time, resulting in greater effectiveness and lower toxicity. Immunotherapeutic agents can also be combined with these NDDSs to achieve the synergic antitumor effect in a multi‐modality therapeutic approach. In this review, NDDSs are harnessed to load multiple agents to induce ICD by chemotherapy, PDT, PTT, and RT in combination of immunotherapy to promote the therapeutic effect and reduce side effects associated with cancer treatment.

A Noble AuPtAg‐GOx Nanozyme for Synergistic Tumor Immunotherapy Induced by Starvation Therapy‐Augmented Mild Photothermal Therapy

“…It has been reported that the immunogenic cell death (ICD) is an important trigger for anti‐tumor immune responses in vivo. [ 29 ] The ICD induced by AuPtAg‐GOx was examined through measuring the release of three markers, ATP, calreticulin (CRT), and high mobility group box 1 (HMGB‐1). Compared with the control group, the AuPtAg‐GOx + 1064 nm group showed significant ATP release (Figure S24 , Supporting Information), HMGB‐1 release (Figure S25 , Supporting Information), and CRT exposure (Figure S26 , Supporting Information), indicating that AuPtAg‐GOx can effectively promote ICD under laser irradiation.…”

Nanocarrier Co-formulation for Delivery of a TLR7 Agonist plus an Immunogenic Cell Death Stimulus Triggers Effective Pancreatic Cancer Chemo-immunotherapy

“…In addition to chemotherapy-induced immunogenic cell death, there are also radiation or other physical stimuli that can be used to induce ICD (also referred to as an abscopal effect). This includes therapeutic modalities such as radiotherapy (RT), photothermal therapy (PTT), and photodynamic therapy (PDT), which are all currently used for boosting immunotherapy . RT has been shown to induce the expression of CRT, HMGB1, and HSP 70 on the surface of dying tumor cells toward accomplishing an abscopal therapeutic effect. , PTT is capable of killing tumor cells through a hyperthermia response that leads to DNA damage, protein denaturation, and disruption of the cellular membrane.…”

Immunogenic cell death-related classifications in breast cancer identify precise immunotherapy biomarkers and enable prognostic stratification

“…As a form of cell death that can cause an immune response, ICD can stimulate or release immunoregulatory properties while tumor cells die and multiple immune pathways to promote immune responses ( Sansone et al, 2021 ). The current low response rate and multiple side effects of tumor immunotherapy can hopefully be solved by inducing ICD ( Li et al, 2022 ). ICD can not only reverse the microenvironment of tumor immunosuppression but also improve the sensitivity of immunotherapy.…”