Tumour-intrinsic resistance to immune checkpoint blockade

Nature reviews. Immunology, Journal Year: 2019, Volume and Issue: 20(1), P. 25 - 39

Published: Sept. 30, 2019

Language: Английский

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Cancer nanomedicine for combination cancer immunotherapy

Nature Reviews Materials, Journal Year: 2019, Volume and Issue: 4(6), P. 398 - 414

Published: April 26, 2019

Language: Английский

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Radiotherapy toxicity

Nature Reviews Disease Primers, Journal Year: 2019, Volume and Issue: 5(1)

Published: Feb. 21, 2019

Language: Английский

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Safety and Clinical Activity of Pembrolizumab and Multisite Stereotactic Body Radiotherapy in Patients With Advanced Solid Tumors

Journal of Clinical Oncology, Journal Year: 2018, Volume and Issue: 36(16), P. 1611 - 1618

Published: Feb. 13, 2018

Purpose Stereotactic body radiotherapy (SBRT) may stimulate innate and adaptive immunity to augment immunotherapy response. Multisite SBRT is an emerging paradigm for treating metastatic disease. Anti-PD-1–treatment outcomes be improved with lower disease burden. In this context, we conducted a phase I study evaluate the safety of pembrolizumab multisite in patients solid tumors. Patients Methods progressing on standard treatment received two four metastases. Not all metastases were targeted, > 65 mL partially irradiated. dosing varied by site ranged from 30 50 Gy three five fractions predefined dose de-escalation if excess dose-limiting toxicities observed. Pembrolizumab was initiated within 7 days after completion SBRT. Pre- post-SBRT biopsy specimens analyzed subset quantify interferon-γ–induced gene expression. Results A total 79 enrolled; did not receive any only included analysis treated at least one cycle pembrolizumab. Most (94.5%) Median follow-up toxicity 5.5 months (interquartile range, 3.3 8.1 months). Six experienced no radiation reductions. 68 imaging follow-up, overall objective response rate 13.2%. survival 9.6 (95% CI, 6.5 undetermined) median progression-free 3.1 2.9 3.4 Expression interferon-γ–associated genes post–SBRT tumor significantly correlated nonirradiated Conclusion followed well tolerated acceptable toxicity. Additional studies exploring clinical benefit predictive biomarkers combined PD-1–directed are warranted.

Language: Английский

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A general strategy towards personalized nanovaccines based on fluoropolymers for post-surgical cancer immunotherapy

Nature Nanotechnology, Journal Year: 2020, Volume and Issue: 15(12), P. 1043 - 1052

Published: Nov. 2, 2020

Language: Английский

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Manganese Oxide Nanomaterials: Synthesis, Properties, and Theranostic Applications

Advanced Materials, Journal Year: 2020, Volume and Issue: 32(10)

Published: Jan. 28, 2020

Abstract Despite the comprehensive applications in bioimaging, biosensing, drug/gene delivery, and tumor therapy of manganese oxide nanomaterials (MONs including MnO 2 , MnO, Mn O 3 4 x ) their derivatives, a review article focusing on MON‐based nanoplatforms has not been reported yet. Herein, representative progresses MONs synthesis, heterogene, properties, surface modification, toxicity, imaging, biodetection, are mainly introduced. First, five kinds primary synthetic methods presented, thermal decomposition method, exfoliation strategy, permanganates reduction adsorption–oxidation hydro/solvothermal. Second, preparations hollow composite materials summarized specially. Then, chemical toxicity discussed. Next, diagnostic imaging sensing outlined. Finally, some rational designs photodynamic therapy, photothermal chemodynamic sonodynamic radiotherapy, magnetic hyperthermia, chemotherapy, gene starvation ferroptosis, immunotherapy, various combination highlighted.

Language: Английский

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Tumor Microenvironment as A “Game Changer” in Cancer Radiotherapy

International Journal of Molecular Sciences, Journal Year: 2019, Volume and Issue: 20(13), P. 3212 - 3212

Published: June 29, 2019

Radiotherapy (RT), besides cancer cells, also affects the tumor microenvironment (TME): blood vessels and cells of immune system. It damages endothelial causes radiation-induced inflammation. Damaged inhibit infiltration CD8+ T lymphocytes into tumors, immunosuppressive pathways are activated. They lead to accumulation radioresistant suppressor including tumor-associated macrophages (TAMs) with M2 phenotype, myeloid-derived (MDSCs), regulatory (Tregs). The area hypoxia increases. Hypoxia reduces oxygen-dependent DNA damage weakens anti-cancer RT effect. activates formation new leads relapse after irradiation. Irradiation may activate response through immunogenic cell death induction. This "in situ" vaccination In this article, we review how changes in TME affect anticancer efficacy. There is a very delicate balance between activation system immunosuppression induced by RT. effects doses on reactions vascularization remain unclear. A better understanding these interactions will contribute optimization treatment, which prevent recurrence cancer.

Language: Английский

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Charged-particle therapy in cancer: clinical uses and future perspectives

Nature Reviews Clinical Oncology, Journal Year: 2017, Volume and Issue: 14(8), P. 483 - 495

Published: March 14, 2017

Language: Английский

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Host STING-dependent MDSC mobilization drives extrinsic radiation resistance

Nature Communications, Journal Year: 2017, Volume and Issue: 8(1)

Published: Nov. 17, 2017

Abstract Radiotherapy induces and promotes innate adaptive immunity in which host STING plays an important role. However, radioresistance irradiated tumors can also develop, resulting relapse. Here we report a mechanism by extrinsic resistance develops after local ablative radiation that relies on the immunosuppressive action of STING. The STING/type I interferon pathway enhances suppressive inflammation recruiting myeloid cells part via CCR2 pathway. Germ-line knockouts or treatment with anti-CCR2 antibody results blockade radiation-induced MDSC infiltration. Treatment alleviates immunosuppression following activation pathway, enhancing anti-tumor effects agonists radiotherapy. We propose is due to (monocytic) M-MDSC infiltration, tumor radioresistance. Furthermore, radiotherapy be abrogated humans translational strategy involving improve

Language: Английский

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Roles of PD-1/PD-L1 Pathway: Signaling, Cancer, and Beyond

Advances in experimental medicine and biology, Journal Year: 2020, Volume and Issue: unknown, P. 33 - 59

Published: Jan. 1, 2020

Language: Английский

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