Hypoxia as a driver of resistance to immunotherapy

Drug Resistance Updates, Год журнала: 2021, Номер 59, С. 100787 - 100787

Опубликована: Ноя. 18, 2021

Язык: Английский

---

Hypoxia: The Cornerstone of Glioblastoma

International Journal of Molecular Sciences, Год журнала: 2021, Номер 22(22), С. 12608 - 12608

Опубликована: Ноя. 22, 2021

Glioblastoma is the most aggressive form of brain tumor in adults and characterized by presence hypervascularization necrosis, both caused a hypoxic microenvironment. In this review, we highlight that hypoxia-induced factor 1 (HIF-1), main activated hypoxia, an important driver progression GB patients. HIF-1α transcription regulated or absence O2. The expression HIF-1 has been related to high-grade gliomas behavior. promotes via activation angiogenesis, immunosuppression, metabolic reprogramming, promoting cell invasion survival. Moreover, GB, not solely modulated oxygen but also oncogenic signaling pathways, such as MAPK/ERK, p53, PI3K/PTEN. Therefore, inhibition hypoxia pathway could represent treatment alternative disease with very few therapy options. Here, review roles inhibitors have studied thus far, aim shedding light on devastating disease.

Язык: Английский

---

Hypoxia induces HIF1α-dependent epigenetic vulnerability in triple negative breast cancer to confer immune effector dysfunction and resistance to anti-PD-1 immunotherapy

Nature Communications, Год журнала: 2022, Номер 13(1)

Опубликована: Июль 15, 2022

Abstract The hypoxic tumor microenvironment has been implicated in immune escape, but the underlying mechanism remains elusive. Using an vitro culture system modeling human T cell dysfunction and exhaustion triple-negative breast cancer (TNBC), we find that hypoxia suppresses effector gene expression, including NK cells, resulting resistance to immunotherapy. We demonstrate hypoxia-induced factor 1α (HIF1α) interaction with HDAC1 concurrent PRC2 dependency causes chromatin remolding epigenetic suppression of genes subsequent dysfunction. Targeting HIF1α associated machinery can reverse overcome PD-1 blockade, as demonstrated both vivo using syngeneic humanized mice models. These findings identify a HIF1α-mediated provide potential strategy TNBC.

Язык: Английский

---

Role of hypoxia in the tumor microenvironment and targeted therapy

Frontiers in Oncology, Год журнала: 2022, Номер 12

Опубликована: Сен. 23, 2022

Tumor microenvironment (TME), which is characterized by hypoxia, widely exists in solid tumors. As a current research hotspot the TME, hypoxia expected to become key element break through bottleneck of tumor treatment. More and more results show that variety biological behaviors cells are affected many factors TME closely related hypoxia. In order inhibiting immune response plays an important role cell metabolism anti-apoptosis. Therefore, exploring molecular mechanism mediated malignant behavior therapeutic targets provide new ideas for anti-tumor therapy. this review, we discussed effects on its interaction with from perspectives cells, metabolism, oxidative stress inducible factor (HIF), listed or signal pathways found so far. Finally, summarize therapies targeting such as glycolysis inhibitors, anti-angiogenesis drugs, HIF hypoxia-activated prodrugs, hyperbaric medicine.

Язык: Английский

---

Tumour hypoxia in driving genomic instability and tumour evolution

Nature reviews. Cancer, Год журнала: 2025, Номер unknown

Опубликована: Янв. 28, 2025

Язык: Английский

---

Advances in the understanding and therapeutic manipulation of cancer immune responsiveness: a Society for Immunotherapy of Cancer (SITC) review

Journal for ImmunoTherapy of Cancer, Год журнала: 2025, Номер 13(1), С. e008876 - e008876

Опубликована: Янв. 1, 2025

Cancer immunotherapy-including immune checkpoint inhibition (ICI) and adoptive cell therapy (ACT)-has become a standard, potentially curative treatment for subset of advanced solid liquid tumors. However, most patients with cancer do not benefit from the rapidly evolving improvements in understanding principal mechanisms determining responsiveness (CIR); including patient-specific genetically determined acquired factors, as well intrinsic biology. Though CIR is multifactorial, fundamental concepts are emerging that should be considered design novel therapeutic strategies related clinical studies. Recent advancements approaches to address limitations current treatments discussed here, specific focus on ICI ACT.

Язык: Английский

---

Tumour Hypoxia-Mediated Immunosuppression: Mechanisms and Therapeutic Approaches to Improve Cancer Immunotherapy

Cells, Год журнала: 2021, Номер 10(5), С. 1006 - 1006

Опубликована: Апрель 24, 2021

The magnitude of the host immune response can be regulated by either stimulatory or inhibitory checkpoint molecules. Receptor-ligand binding between molecules is often exploited tumours to suppress anti-tumour responses. Immune inhibitors that block these interactions relieve T-cells from negative regulation, and have yielded remarkable activity in clinic. Despite this success, clinical data reveal durable responses are limited a minority patients malignancies, indicating presence underlying resistance mechanisms. Accumulating evidence suggests tumour hypoxia, pervasive feature many solid cancers, critical phenomenon involved suppressing generated inhibitors. In review, we discuss mechanisms associated with hypoxia-mediate immunosuppression focus on modulating hypoxia as an approach improve immunotherapy responsiveness.

Язык: Английский

---

Improving CAR T-Cell Persistence

International Journal of Molecular Sciences, Год журнала: 2021, Номер 22(19), С. 10828 - 10828

Опубликована: Окт. 7, 2021

Over the last decade remarkable progress has been made in enhancing efficacy of CAR T therapies. However, clinical benefits are still limited, especially solid tumors. Even hematological settings, patients that respond to therapies remain at risk relapsing due several factors including poor T-cell expansion and lack long-term persistence after adoptive transfer. This issue is even more evident tumors, as tumor microenvironment negatively influences survival, infiltration, activity T-cells. Limited remains a significant hindrance development effective determinants, which encountered from cell manufacturing step onwards. design ex vivo manipulation, culture conditions, may play pivotal role. Moreover, previous chemotherapy lymphodepleting treatments relevant In this review, main causes for decreased T-cells will be discussed, focusing on molecular mechanisms underlying exhaustion. The approaches taken so far overcome these limitations create exhaustion-resistant described. We also examine knowledge gained key trials highlight determining stemness, promoting stemness represent an attractive approach improve

Язык: Английский

---

Crosstalk between angiogenesis and immune regulation in the tumor microenvironment

Archives of Pharmacal Research, Год журнала: 2022, Номер 45(6), С. 401 - 416

Опубликована: Июнь 1, 2022

Cancer creates a complex tumor microenvironment (TME) composed of immune cells, stromal blood vessels, and various other cellular extracellular elements. It is essential for the development anti-cancer combination therapies to understand overcome this high heterogeneity complexity as well dynamic interactions between them within TME. Recent treatment strategies incorporating immune-checkpoint inhibitors anti-angiogenic agents have brought many changes advances in clinical cancer treatment. However, there are still challenges suppressive tumors, which characterized by lack T cell infiltration resistance. In review, we will investigate crosstalk immunity angiogenesis addition, look at designed enhance immunity, convert "immune tumors" into activating tumors," mechanisms these effector infiltration.

Язык: Английский

---

Targeting HIF-2α in the Tumor Microenvironment: Redefining the Role of HIF-2α for Solid Cancer Therapy

Cancers, Год журнала: 2022, Номер 14(5), С. 1259 - 1259

Опубликована: Фев. 28, 2022

Inadequate oxygen supply, or hypoxia, is characteristic of the tumor microenvironment and correlates with poor prognosis therapeutic resistance. Hypoxia leads to activation hypoxia-inducible factor (HIF) signaling pathway stabilization HIF-α subunit, driving progression. The homologous alpha subunits, HIF-1α HIF-2α, are responsible for mediating transcription a multitude critical proteins that control proliferation, angiogenic signaling, metastasis, other oncogenic factors, both differentially sequentially regulating hypoxic response. Post-translational modifications HIF play central role in its behavior as mediator transcription, well temporal transition from HIF-2α occurs response chronic hypoxia. While it evident highly dynamic, remains vastly under-considered. can intensify behaviors most aggressive tumors by adapting cell oxidative stress, thereby promoting tissue remodeling, angiogenesis, upregulating cancer stem factors. structure, function, response, spatiotemporal dynamics, roles progression persistence this molecule

Язык: Английский

---