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Combination therapy with proteasome inhibitors and TLR agonists enhances tumour cell death and IL-1? production.

ABSTRACT: Proteasome inhibitors have emerged as an effective therapy for the treatment of haematological malignancies; however, their efficacy can be limited by the development of tumour resistance mechanisms. Novel combination strategies including the addition of TLR adjuvants to increase cell death and augment immune responses may help enhance their effectiveness. Although generally thought to inhibit inflammatory responses and NF-?B activation, we found that under specific conditions proteasome inhibitors can promote inflammatory responses by mediating IL-1? maturation and secretion after TLR stimulation. This was dependent on the timing of proteasome inhibition relative to TLR stimulation where reversal of treatment order could alternatively increase or inhibit IL-1? secretion (P?

SUBMITTER: Tang AC

PROVIDER: S-EPMC5833743 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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Combination therapy with proteasome inhibitors and TLR agonists enhances tumour cell death and IL-1β production.

Tang Anthony C AC Rahavi Seyed M SM Fung Shan-Yu SY Lu Henry Y HY Yang Hong H Lim Chinten J CJ Reid Gregor S GS Turvey Stuart E SE

Cell death & disease 20180207 2

Proteasome inhibitors have emerged as an effective therapy for the treatment of haematological malignancies; however, their efficacy can be limited by the development of tumour resistance mechanisms. Novel combination strategies including the addition of TLR adjuvants to increase cell death and augment immune responses may help enhance their effectiveness. Although generally thought to inhibit inflammatory responses and NF-κB activation, we found that under specific conditions proteasome inhibit ...[more]

PMID: 29415982

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