Regulatory T cells as crucial trigger and potential target for hyperprogressive disease subsequent to PD-1/PD-L1 blockade for cancer treatment

Ren, Zhe; Yang, Kaiqing; Zhu, Lin; Yin, Detao; Zhou, Yubing

doi:10.1016/j.intimp.2024.111934

International Immunopharmacology

2024

DOI: 10.1016/j.intimp.2024.111934

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Regulatory T cells as crucial trigger and potential target for hyperprogressive disease subsequent to PD-1/PD-L1 blockade for cancer treatment

Zhe Ren,

Kaiqing Yang,

Lin Zhu

et al.

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Cited by 3 publications

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Ni‐MOF Engineered System Targeting Macrophage Aurora A Kinase for Bone Loss Prevention Through PD‐L1 Activation

Zhang,

et al. 2024

Adv Funct Materials

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Postmenopausal bone loss due to estrogen deficiency necessitates effective therapeutic strategies. Our study explores targeting macrophage Aurora A kinase to mitigate bone loss. Aurora A kinase phosphorylation is observed being increased in bone marrow‐derived macrophages (BMDMs) from ovariectomy (OVX) mice, along with a reduction in programmed death‐ligand 1 (PD‐L1) expression. Detailed analysis reveals that PD‐L1 plays an immunomodulatory role by lowering the ratio of T helper 17 cells and regulatory T cells. The metabolic shift toward glycolysis through transcriptome sequencing, induced by Aurora A kinase inhibition, is essential for PD‐L1 expression in BMDMs. The interaction between Aurora A kinase and cytochrome C oxidase subunit 5B is found to enhance PD‐L1 expression. To apply these findings therapeutically, a multifunctional system is developed using a Nickel‐metal organic framework combined with bisphosphonate and MLN8237 (BP@Ni‐MOF/MLN8237). This system targets bone tissues through bisphosphonate and effectively delivers MLN8237 to macrophages, promoting PD‐L1 expression for a favorable immune environment. Moreover, this system exhibits an obvious angiogenic effect. The present study highlights the crucial roles of macrophage Aurora A kinase and PD‐L1 in maintaining bone homeostasis as well as the angiogenesis effect by Ni‐MOF engineered system, presenting a promising therapeutic approach to prevent postmenopausal bone loss.

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Ni‐MOF Engineered System Targeting Macrophage Aurora A Kinase for Bone Loss Prevention Through PD‐L1 Activation

Zhang,

et al. 2024

Adv Funct Materials

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Traditional Chinese medicine and its components effectively reduce resistance mediated by immune checkpoint inhibitors

Guo,

Fang,

2024

Front. Immunol.

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Immunotherapy has become a global focus in cancer treatment and research, with promising results from targeting immune checkpoints in tumors like non-small cell lung cancer, colon cancer, and melanoma. However, resistance to immune checkpoint inhibitors (ICIs) remains a significant challenge. Traditional Chinese medicine (TCM), known for its low toxicity and minimal side effects, shows promise in enhancing cancer treatment when combined with modern therapies. This study reviews recent research on ICIs resistance mechanisms and highlights TCM’s potential in overcoming this resistance, aiming to improve ICIs efficacy while minimizing toxicity.

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Case report: Fast disease progression during adjuvant therapy with anti-PD-1 in stage III melanoma patients

Di Pietro,

Verkhovskaia,

Falcone

et al. 2024

Front. Oncol.

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BackgroundStage III surgically resected melanoma is a disease at high risk of recurrence. Immune checkpoint inhibitors (ICIs) and the target therapy with BRAF and MEK inhibitors significantly changed the outcome of patients with metastatic melanoma and several studies have also shown their benefit in the adjuvant setting for the delay of recurrence in stage III melanoma patients. Hyperprogression disease was observed as a possible adverse response to immunotherapy in the metastatic setting, suggesting that some patients could face additional risk of progression with ICIs, although no consensus was found for the correct definition of this event.Case presentationWe describe here two cases of rapid multiorgan metastatization during adjuvant immunotherapy in patients with stage III resected melanoma. Even though it would be not accurate to define this syndrome as hyperprogression because of apparent absence of the initial disease in the adjuvant setting, we observed in these two cases the same very rapid progression after first administration of adjuvant ICIs that resulted in death of patients within two months from the starting of treatment. Both patients had NRAS mutated melanoma.ConclusionThere is an urgent need for a better understanding of the causes of these fatal outcomes and for the identification of biomarkers that would allow to select the patients before offering them an adjuvant treatment, reducing the risk of hyperprogression. From these cases, we suggest that it could be useful a particular attention in proposing ICI adjuvant treatment based on the molecular profile.

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Regulatory T cells as crucial trigger and potential target for hyperprogressive disease subsequent to PD-1/PD-L1 blockade for cancer treatment

Cited by 3 publications

References 116 publications

Ni‐MOF Engineered System Targeting Macrophage Aurora A Kinase for Bone Loss Prevention Through PD‐L1 Activation

Ni‐MOF Engineered System Targeting Macrophage Aurora A Kinase for Bone Loss Prevention Through PD‐L1 Activation

Traditional Chinese medicine and its components effectively reduce resistance mediated by immune checkpoint inhibitors

Case report: Fast disease progression during adjuvant therapy with anti-PD-1 in stage III melanoma patients

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