2018
DOI: 10.1186/s40425-018-0457-0
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PI3Kα/δ inhibition promotes anti-tumor immunity through direct enhancement of effector CD8+ T-cell activity

Abstract: PI3K inhibitors with differential selectivity to distinct PI3K isoforms have been tested extensively in clinical trials, largely to target tumor epithelial cells. PI3K signaling also regulates the immune system and inhibition of PI3Kδ modulate the tumor immune microenvironment of pre-clinical mouse tumor models by relieving T-regs-mediated immunosuppression. PI3K inhibitors as a class and PI3Kδ specifically are associated with immune-related side effects. However, the impact of mixed PI3K inhibitors in tumor i… Show more

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Cited by 73 publications
(72 citation statements)
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References 38 publications
(71 reference statements)
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“…During T-cell activation, Src homology 2 domain-containing leukocyte protein of 76 kDa (SLP76) associates with PI3K subunit p85, leading to the downstream Akt activation (8). Inhibition of PI3K isoform promoted robust CD8 þ T-cell activation, improved antitumor immunity, and host survival by enhancing the cytokines production of cytotoxic lymphocytes (9,10). PI3K/Akt/mTOR complex has also been shown to be involved in the differentiation of various immunosuppressive T-cell subsets including Foxp3 þ Treg cell and tumor-associated macrophages (11,12).…”
Section: Introductionmentioning
confidence: 99%
“…During T-cell activation, Src homology 2 domain-containing leukocyte protein of 76 kDa (SLP76) associates with PI3K subunit p85, leading to the downstream Akt activation (8). Inhibition of PI3K isoform promoted robust CD8 þ T-cell activation, improved antitumor immunity, and host survival by enhancing the cytokines production of cytotoxic lymphocytes (9,10). PI3K/Akt/mTOR complex has also been shown to be involved in the differentiation of various immunosuppressive T-cell subsets including Foxp3 þ Treg cell and tumor-associated macrophages (11,12).…”
Section: Introductionmentioning
confidence: 99%
“… 6 This dosing of PI-3065 was subsequently validated by others to provide selectivity for PI3Kδ. 22 Vehicle treated mice were given an equivalent volume of carrier solution. Mice were dosed daily either from day −1 prior to tumor inoculation or from day 7 after tumor inoculation until the termination of the experiment.…”
Section: Methodsmentioning
confidence: 99%
“…Regorafenib promoted apoptosis and NF‐κB activation in human CRC models, 81,82 and enhanced antitumor immunity in mCRC patients 83 . PI3Kα/δ inhibition was shown to promote antitumor immunity through direct enhancement of effector CD8(+) T‐cell activity in the CT‐26 syngeneic model 84 …”
Section: Icd‐inducing Agents In Crc Prevention and Therapymentioning
confidence: 97%