2. Academic Validation
  3. Biomaterial-mediated modulation of oral microbiota synergizes with PD-1 blockade in mice with oral squamous cell carcinoma

Biomaterial-mediated modulation of oral microbiota synergizes with PD-1 blockade in mice with oral squamous cell carcinoma

  • Nat Biomed Eng. 2022 Jan;6(1):32-43. doi: 10.1038/s41551-021-00807-9.
Di-Wei Zheng  # 1,  Wei-Wei Deng  # 2,  Wen-Fang Song 1,  Cong-Cong Wu 2,  Jie Liu 2,  Sheng Hong 1,  Ze-Nan Zhuang 1,  Han Cheng 1,  Zhi-Jun Sun 3,  Xian-Zheng Zhang 4
Affiliations

Affiliations

  • 1 Key Laboratory of Biomedical Polymers of Ministry of Education & Department of Chemistry, Wuhan University, Wuhan, P. R. China.
  • 2 The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education & Department of Oral Maxillofacial Head Neck Oncology, School and Hospital of Stomatology, Wuhan University, Wuhan, P. R. China.
  • 3 The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education & Department of Oral Maxillofacial Head Neck Oncology, School and Hospital of Stomatology, Wuhan University, Wuhan, P. R. China. sunzj@whu.edu.cn.
  • 4 Key Laboratory of Biomedical Polymers of Ministry of Education & Department of Chemistry, Wuhan University, Wuhan, P. R. China. xz-zhang@whu.edu.cn.
  • # Contributed equally.
PMID: 34750535 DOI: 10.1038/s41551-021-00807-9
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.

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