Related Experiment Video
Updated: Jul 17, 2026
Immunophenotyping of Orthotopic Homograft Syngeneic of Murine Primary KPC Pancreatic Ductal Adenocarcinoma by Flow Cytometry
Published on: October 9, 2018
The effect of immunotherapy PD-1 blockade on acute bone cancer pain: Insights from transcriptomic and microbiomic
Ruifeng Ding1, Jinfang Lu1, Xingshuai Huang1
1Department of Anesthesiology, Changzheng Hospital, Second Affiliated Hospital of Naval Medical University, Shanghai 200003, China.
Introduction:
The skeletal system ranks as the third most common site for cancer metastasis, often leading to pain with nociceptive and neuropathic features. Programmed cell death protein 1 (PD-1)-targeting therapeutic antibodies offer effective cancer treatment but can cause treatment-related acute pain. Understanding the mechanisms of this pain and identifying potential interventions is still a challenge.
Methods:
A murine model of bone cancer pain was established using Lewis lung carcinoma (LLC) cells, followed by intravenous administration of nivolumab, a human anti-PD-1 monoclonal antibody. Pain thresholds were measured, and micro-CT images of the skeletal system were obtained. High-throughput sequencing of the spinal cord/colon transcriptome during the acute phase of bone cancer pain and gut microbiota analysis at the end of the treatment were performed. Immunofluorescence staining and western blot experiments assessed spinal cord microglia activation and acute pain-associated molecules.
Results:
PD-1 inhibition with nivolumab protected against bone degradation initiated by LLC cell administration but consistently induced acute pain during nivolumab treatment. Spinal cord and colon transcriptomics revealed an immunopathological pattern during tumor progression and the acute pain phase, with notable changes in interleukin and S100 gene families. Gut microbiota analysis post-immunotherapy showed a decline in beneficial bacteria associated with short-chain fatty acid (SCFA) production. Activation of spinal cord microglia and enhanced glycolytic metabolism were confirmed as key factors in inducing acute pain following immunotherapy.
Conclusions:
This study reveals that nivolumab induces acute pain by activating microglia and enhancing glycolytic metabolism in the treatment of bone cancer and uncovers connections between transcriptomic changes, gut microbiota, and acute pain following immune checkpoint blockade (ICB) treatment. It offers novel insights into the relationship between immune checkpoint blockade therapies and pain management.
Insights
Immune checkpoint blockade therapy with nivolumab can cause acute pain by activating spinal cord microglia and altering gut bacteria. This study reveals mechanisms linking immunotherapy, gut microbiome, and pain in bone cancer.
Area of Science:
- Oncology
- Immunology
- Neuroscience
Background:
- Bone metastasis is a common cancer complication causing significant pain.
- Immunotherapy targeting Programmed cell death protein 1 (PD-1) is effective but can induce treatment-related pain.
- Mechanisms underlying this pain and potential interventions remain unclear.
Purpose of the Study:
- To investigate the mechanisms of acute pain induced by anti-PD-1 therapy in a bone cancer model.
- To explore the relationship between immunotherapy, spinal cord changes, and gut microbiota.
Main Methods:
- Established a murine model of bone cancer pain using Lewis lung carcinoma (LLC) cells.
- Administered nivolumab (anti-PD-1 antibody) and assessed pain thresholds.
- Analyzed spinal cord/colon transcriptome, gut microbiota, microglia activation, and pain-associated molecules.
Main Results:
- Nivolumab protected against bone degradation but induced acute pain.
- Transcriptomics showed immunopathological patterns and changes in interleukin and S100 genes.
- Spinal cord microglia activation and enhanced glycolytic metabolism were key pain drivers, linked to gut microbiota alterations.
Conclusions:
- Nivolumab induces acute pain via microglia activation and enhanced glycolytic metabolism in bone cancer treatment.
- Identified links between transcriptomic changes, gut microbiota, and pain following immune checkpoint blockade (ICB).
- Provides insights into pain management strategies for ICB therapies.
Related Concept Videos
02:57Targeted Cancer Therapies
There are several types of targeted therapies against specific...
01:27Tumor Immunotherapy