Reinforcing the immunogenic cell death to enhance cancer immunotherapy efficacy

Yu, Sihui; Xiao, Hongyang; Ma, Li; Zhang, Jiawen; Zhang, Jiarong

doi:10.1016/j.bbcan.2023.188946

Cited by 9 publications

(4 citation statements)

References 259 publications

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“…31 ICD represents a particular form of cancer cell death accompanied by production of DAMPs that can be recognized by pattern recognition receptors, which enhances infiltration of effector T cells and potentiates anti-tumor immune responses. 32 The abnormal functioning of ICD inevitably leads to an imbalance in the anti-tumor effect, consequently contributing to the occurrence and progression of HCC. The most direct cause of this imbalance is the differential expression of ICD-related genes.…”

Section: Discussionmentioning

confidence: 99%

Construction of an Immunogenic Cell Death-Related Gene Signature and Genetic Subtypes for Predicting Prognosis, Immune Microenvironments, and Drug Sensitivity in Hepatocellular Carcinoma

Li,

Zhang,

Sun

et al. 2024

JIR

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Immunogenic cell death (ICD) is a type of regulated cell death that modifies the immune response by releasing DAMPs or danger signals. Herein, we aimed to develop an ICD-related predictive model for patients with hepatocellular carcinoma (HCC) and investigate its applicability for predicting prognostic outcomes and immunotherapeutic responses. Methods: Differentially expressed genes of ICD were identified in the HCC and normal liver samples. A prognostic risk model and a nomogram containing clinicopathological features were created. To validate the effectiveness of the model, an external dataset was used. Clinical characteristics, prognosis, tumor mutation burden, immune microenvironments, biological function and chemotherapeutic drug sensitivity were evaluated for different genetic subtypes and risk groups. Results: A total of 35 ICD-related genes (ICDRGs) were identified between HCC and normal samples, 11 of which were significantly associated with overall survival (OS) in HCC patients. Four different genetic subtypes were formed and eight ICDRGs were selected to develop a risk prognostic model. The risk scores were shown to be an independent prognostic factor for HCC and positively correlated with pathological severity. Patients in the high-risk group had a higher frequency of TP53 mutations, increased expression of immune checkpoints and human leukocyte antigen genes. The inhibitory concentrations of chemotherapeutic drugs differed in different populations. Conclusion:In this study, we developed an ICDRG risk model and demonstrated its applicability in predicting survival outcomes, immune and chemotherapeutic responses in HCC patients. ICDRGs are expected to be used as novel biomarkers in the medical decision-making of HCC.

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Section: Discussionmentioning

confidence: 99%

Construction of an Immunogenic Cell Death-Related Gene Signature and Genetic Subtypes for Predicting Prognosis, Immune Microenvironments, and Drug Sensitivity in Hepatocellular Carcinoma

Li,

Zhang,

Sun

et al. 2024

JIR

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“…To further exploit the indications of existing chemotherapeutic agents, it is necessary to study their role in other aspects, including immunity. ICD is a particular mode of cell death observed during tumor immunogenicity and is different from apoptosis ( 19 ). This phenomenon can be stimulated by certain chemotherapeutic agents.…”

Section: Discussionmentioning

confidence: 99%

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

Zhu,

Zhang,

et al. 2024

Transl Cancer Res

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Background Emerging evidence suggests that immunogenic chemotherapy not only kills tumor cells but also improves the immune-suppressive tumor microenvironment by inducing immunogenic cell death (ICD), leading to sustained anti-tumor effects. The lack of ICD inducers explored in lung cancer necessitates investigation into new inducers for this context, therefore, this study aims to explore whether the gemcitabine (GEM) and celecoxib can activate the immunogenic chemotherapy progress in lung cancer tissue. Methods We assessed five chemotherapeutic agents for their ability to trigger ICD using ex vivo and in vivo experiments, including western blotting (WB), flow cytometry, and tumor preventive vaccine assays. Additionally, we evaluated the synergistic effects of GEM, celecoxib, and anti-programmed death 1 monoclonal antibody (aPD-1) in tumor-bearing mice to understand how GEM activates antitumor immunity and enhances immunochemotherapy. Results GEM was identified as an effective ICD inducer, showing high expression of calreticulin (CRT) and heat shock protein 90 (HSP90). Co-culture with GEM-treated cells [Lewis lung carcinoma (LLC) and CMT-64] enhanced dendritic cell (DC) activity, evidenced by maturation markers and increased phagocytic capacity. Moreover, celecoxib was found to enhance ICD by reducing indoleamine 2,3-dioxygenase 1 (IDO1) expression and increasing reactive oxygen species (ROS)-based endoplasmic reticulum (ER) stress. The combination therapy [GEM, celecoxib, and aPD-1 (GCP)] exhibited potent and sustained antitumor activity in immunocompetent mice, with enhanced recruitment of tumor-infiltrating lymphocytes. Conclusions These findings support the potential use of GCP therapy as a treatment option for lung cancer patients.

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“…The event of tumor cell death that encourages anti-tumor immune responses is known as Immunogenic Cell Death (ICD) ( Yu et al, 2023 ). ICD is a unique form of cell death.…”

Section: Mechanism Of Action Of Nanomedicine Targeting Myeloid Cellsmentioning

confidence: 99%

“…Furthermore, the ability of nanomaterials to induce ICD is used to enhance the therapeutic effect of combination anti-tumor drug therapy, either by encapsulating multiple drugs in the same particle to ensure joint delivery to target cells or by combining the drugs with synergistic interaction modes to produce synergistically enhanced anti-tumor effects ( Mishchenko et al, 2019 ; Yu et al, 2023 ). Platinum-based chemotherapy is widely used as a first-line treatment for a variety of cancers.…”

Section: Preclinical and Clinical Research On Nanodrugs Targeting Mye...mentioning

confidence: 99%

Potential targets and applications of nanodrug targeting myeloid cells in osteosarcoma for the enhancement of immunotherapy

Zhu,

Fan,

Xia

et al. 2023

Front. Pharmacol.

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Targeted immunotherapies have emerged as a transformative approach in cancer treatment, offering enhanced specificity to tumor cells, and minimizing damage to healthy tissues. The targeted treatment of the tumor immune system has become clinically applicable, demonstrating significant anti-tumor activity in both early and late-stage malignancies, subsequently enhancing long-term survival rates. The most frequent and significant targeted therapies for the tumor immune system are executed through the utilization of checkpoint inhibitor antibodies and chimeric antigen receptor T cell treatment. However, when using immunotherapeutic drugs or combined treatments for solid tumors like osteosarcoma, challenges arise due to limited efficacy or the induction of severe cytotoxicity. Utilizing nanoparticle drug delivery systems to target tumor-associated macrophages and bone marrow-derived suppressor cells is a promising and attractive immunotherapeutic approach. This is because these bone marrow cells often exert immunosuppressive effects in the tumor microenvironment, promoting tumor progression, metastasis, and the development of drug resistance. Moreover, given the propensity of myeloid cells to engulf nanoparticles and microparticles, they are logical therapeutic targets. Therefore, we have discussed the mechanisms of nanomedicine-based enhancement of immune therapy through targeting myeloid cells in osteosarcoma, and how the related therapeutic strategies well adapt to immunotherapy from perspectives such as promoting immunogenic cell death with nanoparticles, regulating the proportion of various cellular subgroups in tumor-associated macrophages, interaction with myeloid cell receptor ligands, activating immunostimulatory signaling pathways, altering myeloid cell epigenetics, and modulating the intensity of immunostimulation. We also explored the clinical implementations of immunotherapy grounded on nanomedicine.

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Reinforcing the immunogenic cell death to enhance cancer immunotherapy efficacy

Cited by 9 publications

References 259 publications

Construction of an Immunogenic Cell Death-Related Gene Signature and Genetic Subtypes for Predicting Prognosis, Immune Microenvironments, and Drug Sensitivity in Hepatocellular Carcinoma

Construction of an Immunogenic Cell Death-Related Gene Signature and Genetic Subtypes for Predicting Prognosis, Immune Microenvironments, and Drug Sensitivity in Hepatocellular Carcinoma

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

Potential targets and applications of nanodrug targeting myeloid cells in osteosarcoma for the enhancement of immunotherapy

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