- •Combining PD-1 blockade, radiation therapy and phosphoinositide 3-kinaseγδ inhibitor were tested in breast cancer models.
- •Syngenic murine tumour and humanised patient-derived xenograft model were used.
- •The greatest anti-tumour effect was achieved with triple combination therapy.
- •Triple combination increased cytotoxic T-cells and decreased immune-suppressive cells.
- •This strategy could be a viable approach to overcome the therapeutic resistance of PD1 blockade.
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- Durable complete response after discontinuation of pembrolizumab in patients with metastatic melanoma.J Clin Oncol. 2018; 36: 1668-1674
- Atezolizumab for first-line treatment of metastatic nonsquamous NSCLC.N Engl J Med. 2018; 378: 2288-2301
- Time to abandon single-site irradiation for inducing abscopal effects.Nat Rev Clin Oncol. 2019; 16: 123-135https://doi.org/10.1038/s41571-018-0119-7
- Transient regulatory T cell ablation deters oncogene-driven breast cancer and enhances radiotherapy.J Exp Med. 2013; 210: 2435-2466https://doi.org/10.1084/jem.20130762
- Macrophage targeting: opening new possibilities for cancer immunotherapy.Immunology. 2018; 155: 285-293https://doi.org/10.1111/imm.12976
- Targeting myeloid-derived suppressor cells to bypass tumour-induced immunosuppression.Front Immunol. 2018; 9https://doi.org/10.3389/fimmu.2018.00398
- PD-1 blockade induces responses by inhibiting adaptive immune resistance.Nature. 2014; 515: 568-571https://doi.org/10.1038/nature13954
- Immunotherapy resistance: the answers lie ahead - not in front - of us.J Immunother Cancer. 2017; 5https://doi.org/10.1186/s40425-017-0212-y
- The future of immune checkpoint therapy.Science. 2015; 348 (80-): 56-61https://doi.org/10.1126/science.aaa8172
- Immunotherapy for breast cancer: what are we missing?.Clin Canc Res. 2017; 23: 2640-2646https://doi.org/10.1158/1078-0432.CCR-16-2569
- Fractionated but not single-dose radiotherapy induces an immune-mediated abscopal effect when combined with anti-CTLA-4 antibody.Clin Canc Res. 2009; 15: 5379-5388https://doi.org/10.1158/1078-0432.CCR-09-0265
- Immune-mediated inhibition of metastases after treatment with local radiation and CTLA-4 blockade in a mouse model of breast cancer.Clin Canc Res. 2005; 11: 728-734
- Radiotherapy combination opportunities leveraging immunity for the next oncology practice.CA Cancer J Clin. 2017; 67: 65-85https://doi.org/10.3322/caac.21358
- Radiotherapy and immunotherapy: a beneficial liaison?.Nat Rev Clin Oncol. 2017; 14: 365-379https://doi.org/10.1038/nrclinonc.2016.211
- PI3K isoform-selective inhibitors: next-generation targeted cancer therapies.Acta Pharmacol Sin. 2015; 36: 1170-1176https://doi.org/10.1038/aps.2015.71
- Inactivation of PI(3)K p110δ breaks regulatory T-cell-mediated immune tolerance to cancer.Nature. 2014; 510: 407-411https://doi.org/10.1038/nature13444
- Overcoming resistance to checkpoint blockade therapy by targeting PI3Kγ in myeloid cells.Nature. 2016; 539: 443-447https://doi.org/10.1038/nature20554
- Human cord blood (hCB)-CD34+ humanised mice fail to reject human acute myeloid leukemia cells.PLoS One. 2019; 14e0217345https://doi.org/10.1371/journal.pone.0217345
- The reactome pathway knowledgebase.Nucleic Acids Res. 2020; https://doi.org/10.1093/nar/gkz1031
- BioCarta.Biotech Softw Internet Rep. 2001; https://doi.org/10.1089/152791601750294344
- Determining cell type abundance and expression from bulk tissues with digital cytometry.Nat Biotechnol. 2019; https://doi.org/10.1038/s41587-019-0114-2
- Immune response to firefly luciferase as a naked DNA.Cancer Biol Ther. 2007; https://doi.org/10.4161/cbt.6.5.4005
- Estimating the population abundance of tissue-infiltrating immune and stromal cell populations using gene expression.Genome Biol. 2016; https://doi.org/10.1186/s13059-016-1070-5
- PI3K isoforms in cell signalling and vesicle trafficking.Nat Rev Mol Cell Biol. 2019; https://doi.org/10.1038/s41580-019-0129-z
- Tumour endothelium FasL establishes a selective immune barrier promoting tolerance in tumours.Nat Med. 2014; 20: 607-615https://doi.org/10.1038/nm.3541
- Resistance to cancer immunotherapy mediated by apoptosis of tumour-infiltrating lymphocytes.Nat Commun. 2017; 8https://doi.org/10.1038/s41467-017-00784-1
- Hyperprogressive disease is a new pattern of progression in cancer patients treated by anti-PD-1/PD-L1.Clin Canc Res. 2017; 23: 1920-1928https://doi.org/10.1158/1078-0432.CCR-16-1741
- Hyperprogressive disease: recognizing a novel pattern to improve patient management.Nat Rev Clin Oncol. 2018; 15: 748-762https://doi.org/10.1038/s41571-018-0111-2
- PI3Kγ is a molecular switch that controls immune suppression.Nature. 2016; 539: 437-442https://doi.org/10.1038/nature19834
- Tumour-intrinsic resistance to immune checkpoint blockade.Nat Rev Immunol. 2019; https://doi.org/10.1038/s41577-019-0218-4
- Radioimmunotherapy for the treatment of head and neck cancer.Lancet Oncol. 2019; 20: e404-e416https://doi.org/10.1016/s1470-2045(19)30306-7
- A translational concept of immuno-radiobiology.Radiother Oncol. 2019; 140: 116-124https://doi.org/10.1016/j.radonc.2019.06.001
- Radiotherapy: changing the Game in Immunotherapy the promise of radiotherapy as a partner for immunotherapy.Trends Cancer. 2017; 2: 286-294https://doi.org/10.1016/j.trecan.2016.05.002
- Using immunotherapy to boost the abscopal effect.Nat Rev Cancer. 2018; 18: 313-322https://doi.org/10.1038/nrc.2018.6
- DNA exonuclease Trex1 regulates radiotherapy-induced tumour immunogenicity.Nat Commun. 2017; 8: 15618https://doi.org/10.1038/ncomms15618
- Abscopal effects with hypofractionated schedules extending into the effector phase of the tumour-specific T-cell response.Int J Radiat Oncol Biol Phys. 2018; https://doi.org/10.1016/j.ijrobp.2018.01.094
- Interferon γ and tumour necrosis factor have a role in tumour regressions mediated by murine CD8+ tumour-infiltrating lymphocytes.J Exp Med. 1991; 173: 647-658https://doi.org/10.1084/jem.173.3.647
- Radiation therapy induces macrophages to suppress T-cell responses against pancreatic tumours in mice.Gastroenterology. 2016; 150: 1659-1672.e5https://doi.org/10.1053/j.gastro.2016.02.070
- PI3K in cancer: divergent roles of isoforms, modes of activation and therapeutic targeting.Nat Rev Cancer. 2015; 15: 7-24https://doi.org/10.1038/nrc3860
- Systematic pan-cancer analysis of tumour purity.Nat Commun. 2015; 6: 1-12https://doi.org/10.1038/ncomms9971
- xCell: digitally portraying the tissue cellular heterogeneity landscape.Genome Biol. 2017; 18: 1-14https://doi.org/10.1186/s13059-017-1349-1