Targeted scavenging of extracellular ROS relieves suppressive immunogenic cell death

Deng, Hongzhang; Yang, Weijing; Zhou, Zijian; Tian, Rui; Lin, Lisen; Ma, Ying; Song, Jibin; Chen, Xiaoyuan

doi:10.1038/s41467-020-18745-6

Cited by 161 publications

(163 citation statements)

References 39 publications

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“…In addition, many problems in tumor metastasis and drug resistance urgently need solved. An immunosuppressive ECM impedes the implementation of effective immunotherapies (154). These cancer therapy obstacles require an advanced NP system that can precisely target the molecular determinants of the ECM.…”

Section: Discussionmentioning

confidence: 99%

Extracellular Matrix: Emerging Roles and Potential Therapeutic Targets for Breast Cancer

Zhao

Zheng

et al. 2021

Front. Oncol.

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Increasing evidence shows that the extracellular matrix (ECM) is an important regulator of breast cancer (BC). The ECM comprises of highly variable and dynamic components. Compared with normal breast tissue under homeostasis, the ECM undergoes many changes in composition and organization during BC progression. Induced ECM proteins, including fibrinogen, fibronectin, hyaluronic acid, and matricellular proteins, have been identified as important components of BC metastatic cells in recent years. These proteins play major roles in BC progression, invasion, and metastasis. Importantly, several specific ECM molecules, receptors, and remodeling enzymes are involved in promoting resistance to therapeutic intervention. Additional analysis of these ECM proteins and their downstream signaling pathways may reveal promising therapeutic targets against BC. These potential drug targets may be combined with new nanoparticle technologies. This review summarizes recent advances in functional nanoparticles that target the ECM to treat BC. Accurate nanomaterials may offer a new approach to BC treatment.

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Section: Discussionmentioning

confidence: 99%

Extracellular Matrix: Emerging Roles and Potential Therapeutic Targets for Breast Cancer

Zhao

Zheng

et al. 2021

Front. Oncol.

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“…However, there is also evidence that ROS can oxidize the danger signal HMGB1 released from dying cells and thereby neutralize its alarmin activity [ 98 ]. A recent study reported that targeted scavenging of extracellular ROS using a tumor ECM targeting nanomaterial can maintain the stimulatory activity of HMGB1 and restore ICD-induced antitumor immunity [ 99 ]. These studies suggest that the level and duration of ROS may determine whether or not ICD can occur and lead to effective antitumor immunity.…”

Section: The Impact Of Oxidative Stress On Immune Cells In the Tmementioning

confidence: 99%

Oxidative Stress in the Tumor Microenvironment and Its Relevance to Cancer Immunotherapy

Aboelella

Brandle

Kim

et al. 2021

Cancers

100

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It has been well-established that cancer cells are under constant oxidative stress, as reflected by elevated basal level of reactive oxygen species (ROS), due to increased metabolism driven by aberrant cell growth. Cancer cells can adapt to maintain redox homeostasis through a variety of mechanisms. The prevalent perception about ROS is that they are one of the key drivers promoting tumor initiation, progression, metastasis, and drug resistance. Based on this notion, numerous antioxidants that aim to mitigate tumor oxidative stress have been tested for cancer prevention or treatment, although the effectiveness of this strategy has yet to be established. In recent years, it has been increasingly appreciated that ROS have a complex, multifaceted role in the tumor microenvironment (TME), and that tumor redox can be targeted to amplify oxidative stress inside the tumor to cause tumor destruction. Accumulating evidence indicates that cancer immunotherapies can alter tumor redox to intensify tumor oxidative stress, resulting in ROS-dependent tumor rejection. Herein we review the recent progresses regarding the impact of ROS on cancer cells and various immune cells in the TME, and discuss the emerging ROS-modulating strategies that can be used in combination with cancer immunotherapies to achieve enhanced antitumor effects.

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“…Besides this direct pathway beginning with ER stress, an important role in ICD is played by reactive oxygen species (ROS), which, however, seem to be a double-edged sword in this process. On one hand, it has been proven that ROS-induced autophagy triggers ER stress [ 55 ], on the other hand, ROS oxidize HMBG-1 and weaken the function of T cells [ 56 ]. In general, ROS are needed for ICD induction, since antioxidants successfully impede ICD, but for the further flow of the ICD process, it is of benefit to remove them from the tumor microenvironment [ 54 , 56 ].…”

Section: Immunogenic Cell Death and Cgsmentioning

confidence: 99%

“…On one hand, it has been proven that ROS-induced autophagy triggers ER stress [ 55 ], on the other hand, ROS oxidize HMBG-1 and weaken the function of T cells [ 56 ]. In general, ROS are needed for ICD induction, since antioxidants successfully impede ICD, but for the further flow of the ICD process, it is of benefit to remove them from the tumor microenvironment [ 54 , 56 ]. To sum up, for ICD induction, ER stress-causing, and ROS-generating compounds must be sought.…”

Section: Immunogenic Cell Death and Cgsmentioning

confidence: 99%

Cardiac Glycosides as Immune System Modulators

2021

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Cardiac glycosides (CGs) are natural steroid compounds occurring both in plants and animals. They are known for long as cardiotonic agents commonly used for various cardiac diseases due to inhibition of Na+/K+-ATPase (NKA) pumping activity and modulating heart muscle contractility. However, recent studies show that the portfolio of diseases potentially treatable with CGs is much broader. Currently, CGs are mostly studied as anticancer agents. Their antiproliferative properties are based on the induction of multiple signaling pathways in an NKA signalosome complex. In addition, they are strongly connected to immunogenic cell death, a complex mechanism of induction of anticancer immune response. Moreover, CGs exert various immunomodulatory effects, the foremost of which are connected with suppressing the activity of T-helper cells or modulating transcription of many immune response genes by inhibiting nuclear factor kappa B. The resulting modulations of cytokine and chemokine levels and changes in immune cell ratios could be potentially useful in treating sundry autoimmune and inflammatory diseases. This review aims to summarize current knowledge in the field of immunomodulatory properties of CGs and emphasize the large area of potential clinical use of these compounds.

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Targeted scavenging of extracellular ROS relieves suppressive immunogenic cell death

Cited by 161 publications

References 39 publications

Extracellular Matrix: Emerging Roles and Potential Therapeutic Targets for Breast Cancer

Extracellular Matrix: Emerging Roles and Potential Therapeutic Targets for Breast Cancer

Oxidative Stress in the Tumor Microenvironment and Its Relevance to Cancer Immunotherapy

Cardiac Glycosides as Immune System Modulators

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