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Intra-tumoral injection of caerin 1 1 and 1 9 peptides in vaccinated TC-1 tumour bearing mice with PD-1 blockade7.95 MB
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Preprint
Intra-tumoral injection of caerin 1.1 and 1.9 peptides in vaccinated TC-1 tumour bearing mice with PD-1 blockade modulates macrophage heterogeneity and the activation of CD8+ T cells in the tumour microenvironment
Research Square, Vol.10 September 2020
Research Square Company
2020
Abstract
Development of a vaccine formula that alters the tumour-infiltrating lymphocytes to be more immune active against a tumour is key to the improvement of clinical responses to immunotherapy. Here, we demonstrate that, in conjunction with E7 antigen specific immunotherapy, and IL-10 and PD-1 blockade, intra-tumoral administration of caerin 1.1 and 1.9 peptides further improves the tumour microenvironment (TME) when compared with injection of a control peptide. We used single cell transcriptomics and mass spectrometry-based proteomics to quantify changes in cellular activity across different cell types within the TME. We show that the injection of caerin 1.1/1.9 increases immune activating macrophages and NK cells, while reducing immunosuppressive macrophages with M2 phenotype, and increased numbers of activated CD8+ T cells with higher populations of memory and effector-memory CD8+ T subsets. Proteomic profiling demonstrated activation of Stat1 modulated apoptosis and production of nitric oxide. Further, computational integration of the proteome with the single cell transcriptome was consistent with deactivation of immune suppressive B cell function following caerin 1.1 and 1.9 treatment.
Details
- Title
- Intra-tumoral injection of caerin 1.1 and 1.9 peptides in vaccinated TC-1 tumour bearing mice with PD-1 blockade modulates macrophage heterogeneity and the activation of CD8+ T cells in the tumour microenvironment
- Authors
- Guoying Ni (Author) - First People's Hospital of FoshanXiaolian Wu (Author) - First People's Hospital of FoshanYing Liu (Author) - First People's Hospital of FoshanHejie Li (Author) - University of the Sunshine Coast, Queensland, GeneCology Research Centre - LegacyShu Chen (Author) - First People's Hospital of FoshanConor Fogarty (Author) - University of the Sunshine Coast, Queensland, Faculty of Arts, Business and LawIan Frazer (Author) - The University of QueenslandGuoqiang Chen (Author) - First People's Hospital of FoshanTianfang Wang (Author) - University of the Sunshine Coast, Queensland, School of Science and Engineering - Legacy
- Publication details
- Research Square, Vol.10 September 2020
- Publisher
- Research Square Company
- Date published
- 2020
- DOI
- 10.21203/rs.3.rs-73533/v1
- ISSN
- 2693-5015
- Copyright note
- This work is licensed under a CC BY 4.0 License.
- Organisation Unit
- School of Science and Engineering - Legacy; University of the Sunshine Coast, Queensland; GeneCology Research Centre - Legacy; School of Science, Technology and Engineering; Centre for Bioinnovation
- Language
- English
- Record Identifier
- 99482291402621
- Output Type
- Preprint
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