Hypoxic Tumor-Derived Exosomal miR-301a Mediates M2 Macrophage Polarization via PTEN/PI3Kγ to Promote Pancreatic Cancer Metastasis

Cancer Research, Journal Year: 2018, Volume and Issue: 78(16), P. 4586 - 4598

Published: June 7, 2018

Exosomes are emerging as important mediators of the cross-talk between tumor cells and microenvironment. However, mechanisms by which exosomes modulate development under hypoxia in pancreatic cancer remain largely unknown. Here, we found that hypoxic derived from activate macrophages to M2 phenotype a HIF1a or HIF2a-dependent manner, then facilitates migration, invasion, epithelial-mesenchymal transition cells. Given have been shown transport miRNAs alter cellular functions, discovered miR-301a-3p was highly expressed enriched cell-derived exosomes. Circulating exosomal levels positively associated with depth lymph node metastasis, late TNM stage, poor prognosis cancer. Hypoxic induced polarization via activation PTEN/PI3Kγ signaling pathway. Coculturing upregulated treated enhanced their metastatic capacity. Collectively, these data indicate generate miR-301a-3p-rich microenvironment, polarize promote malignant behaviors Targeting may provide potential diagnosis treatment strategy for cancer.Significance: These findings identify an miRNA critical microenvironmental prove be target cancer.Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/78/16/4586/F1.large.jpg Cancer Res; 78(16); 4586-98. ©2018 AACR.

Language: Английский

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Mechanisms of Resistance to Immune Checkpoint Blockade: Why Does Checkpoint Inhibitor Immunotherapy Not Work for All Patients?

American Society of Clinical Oncology Educational Book, Journal Year: 2019, Volume and Issue: 39, P. 147 - 164

Published: May 1, 2019

The emergence of immune checkpoint blockade therapies over the last decade has transformed cancer treatment in a wide range tumor types. Unprecedented and durable clinical responses difficult-to-treat histologies have been observed. However, despite these promising long-term responses, majority patients fail to respond blockade, demonstrating primary resistance. Additionally, many those who initially eventually experience relapse secondary acquired Both resistance are result complex constantly evolving interactions between cells system. Many mechanisms characterized date, more continue be uncovered. By elucidating targeting resistance, treatments can tailored improve outcomes. This review will discuss landscape response data, different mechanisms, potential therapeutic strategies overcome

Language: Английский

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Brain immunology and immunotherapy in brain tumours

Nature reviews. Cancer, Journal Year: 2019, Volume and Issue: 20(1), P. 12 - 25

Published: Dec. 5, 2019

Language: Английский

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Combination Cancer Therapy with Immune Checkpoint Blockade: Mechanisms and Strategies

Immunity, Journal Year: 2018, Volume and Issue: 48(3), P. 417 - 433

Published: March 1, 2018

Language: Английский

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Effective combinatorial immunotherapy for castration-resistant prostate cancer

Nature, Journal Year: 2017, Volume and Issue: 543(7647), P. 728 - 732

Published: March 16, 2017

Language: Английский

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