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Biomaterial-mediated modulation of oral microbiota synergizes with PD-1 blockade in mice with oral squamous cell
Di-Wei Zheng1, Wei-Wei Deng2, Wen-Fang Song1
1Key Laboratory of Biomedical Polymers of Ministry of Education & Department of Chemistry, Wuhan University, Wuhan, P. R. China.
Abstract:
Because a host's immune system is affected by host-microbiota interactions, means of modulating the microbiota could be leveraged to augment the effectiveness of cancer therapies. Here we report that patients with oral squamous cell carcinoma (OSCC) whose tumours contained higher levels of bacteria of the genus Peptostreptococcus had higher probability of long-term survival. We then show that in mice with murine OSCC tumours injected with oral microbiota from patients with OSCCs, antitumour responses were enhanced by the subcutaneous delivery of an adhesive hydrogel incorporating silver nanoparticles (which inhibited the growth of bacteria competing with Peptostreptococcus) alongside the intratumoural delivery of the bacterium P. anaerobius (which upregulated the levels of Peptostreptococcus). We also show that in mice with subcutaneous or orthotopic murine OSCC tumours, combination therapy with the two components (nanoparticle-incorporating hydrogel and exogenous P. anaerobius) synergized with checkpoint inhibition with programmed death-1. Our findings suggest that biomaterials can be designed to modulate human microbiota to augment antitumour immune responses.
Insights
Higher levels of Peptostreptococcus bacteria in oral squamous cell carcinoma (OSCC) correlate with better survival. Modulating the oral microbiota with P. anaerobius and silver nanoparticles enhances anti-tumour immunity and synergizes with cancer therapies.
Area of Science:
- Immunology
- Microbiology
- Biomaterials Science
Background:
- Host-microbiota interactions significantly influence the host immune system.
- Modulating the gut microbiota presents a potential strategy to enhance cancer therapies.
- Oral squamous cell carcinoma (OSCC) is a prevalent malignancy where immune responses play a critical role.
Purpose of the Study:
- To investigate the correlation between oral microbiota composition and patient survival in OSCC.
- To explore the potential of modulating the oral microbiota to enhance anti-tumour immune responses.
- To evaluate the synergistic effects of microbiota modulation with existing cancer immunotherapies.
Main Methods:
- Analysis of oral microbiota in OSCC patients and correlation with long-term survival.
- In vivo studies using murine OSCC models with human oral microbiota transplantation.
- Treatment with a hydrogel incorporating silver nanoparticles to inhibit competing bacteria and intratumoural delivery of P. anaerobius.
- Combination therapy assessment with nanoparticle hydrogel, P. anaerobius, and anti-PD-1 checkpoint inhibition.
Main Results:
- Patients with higher levels of Peptostreptococcus in their OSCC tumors showed a greater probability of long-term survival.
- In mice, anti-tumour responses were enhanced by inhibiting competing bacteria and increasing Peptostreptococcus levels.
- Combination therapy synergized with programmed death-1 (PD-1) checkpoint inhibition in murine OSCC models.
Conclusions:
- The abundance of Peptostreptococcus in oral tumors is associated with improved survival in OSCC patients.
- Biomaterial-based strategies can effectively modulate the oral microbiota to augment anti-tumour immune responses.
- Targeted microbiota modulation holds promise for enhancing the efficacy of cancer immunotherapies.
