Unknown

Dataset Information

0

PD-1 blockade inhibits osteoclast formation and murine bone cancer pain.


ABSTRACT: Emerging immune therapy, such as with the anti-programmed cell death-1 (anti-PD-1) monoclonal antibody nivolumab, has shown efficacy in tumor suppression. Patients with terminal cancer suffer from cancer pain as a result of bone metastasis and bone destruction, but how PD-1 blockade affects bone cancer pain remains unknown. Here, we report that mice lacking Pdcd1 (Pd1-/-) demonstrated remarkable protection against bone destruction induced by femoral inoculation of Lewis lung cancer cells. Compared with WT mice, Pd1-/- mice exhibited increased baseline pain sensitivity, but the development of bone cancer pain was compromised in Pd1-/- mice. Consistently, these beneficial effects in Pd1-/- mice were recapitulated by repeated i.v. applications of nivolumab in WT mice, even though nivolumab initially increased mechanical and thermal pain. Notably, PD-1 deficiency or nivolumab treatment inhibited osteoclastogenesis without altering tumor burden. PD-L1 and CCL2 are upregulated within the local tumor microenvironment, and PD-L1 promoted RANKL-induced osteoclastogenesis through JNK activation and CCL2 secretion. Bone cancer upregulated CCR2 in primary sensory neurons, and CCR2 antagonism effectively reduced bone cancer pain. Our findings suggest that, despite a transient increase in pain sensitivity following each treatment, anti-PD-1 immunotherapy could produce long-term benefits in preventing bone destruction and alleviating bone cancer pain by suppressing osteoclastogenesis.

SUBMITTER: Wang K 

PROVIDER: S-EPMC7324182 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

altmetric image

Publications

PD-1 blockade inhibits osteoclast formation and murine bone cancer pain.

Wang Kaiyuan K   Gu Yun Y   Liao Yihan Y   Bang Sangsu S   Donnelly Christopher R CR   Chen Ouyang O   Tao Xueshu X   Mirando Anthony J AJ   Hilton Matthew J MJ   Ji Ru-Rong RR  

The Journal of clinical investigation 20200701 7


Emerging immune therapy, such as with the anti-programmed cell death-1 (anti-PD-1) monoclonal antibody nivolumab, has shown efficacy in tumor suppression. Patients with terminal cancer suffer from cancer pain as a result of bone metastasis and bone destruction, but how PD-1 blockade affects bone cancer pain remains unknown. Here, we report that mice lacking Pdcd1 (Pd1-/-) demonstrated remarkable protection against bone destruction induced by femoral inoculation of Lewis lung cancer cells. Compar  ...[more]

Similar Datasets

| S-EPMC4327386 | biostudies-literature
| S-EPMC4786676 | biostudies-literature
| S-EPMC4661614 | biostudies-literature
| S-EPMC10346360 | biostudies-literature
| S-EPMC4053136 | biostudies-literature
| S-EPMC3872977 | biostudies-other
| S-EPMC3932359 | biostudies-literature
| S-ECPF-GEOD-39494 | biostudies-other
| S-EPMC1518793 | biostudies-literature
2023-09-14 | GSE242789 | GEO