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Intratumoral admini...
Intratumoral administration of pro-inflammatory allogeneic dendritic cells improved the anti-turnor response of systemic anti-CTLA-4 treatment via unleashing a T cell-dependent response
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- Jin, Chuan, 1986- (författare)
- Uppsala universitet,Klinisk immunologi,Science for Life Laboratory, SciLifeLab
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- Ali, Arwa (författare)
- Uppsala universitet,Klinisk immunologi,Science for Life Laboratory, SciLifeLab
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- Iskantar, Alexandros (författare)
- Uppsala universitet,Institutionen för immunologi, genetik och patologi,Science for Life Laboratory, SciLifeLab
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- Fotaki, Grammatiki (författare)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Klinisk immunologi
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- Wang, Hai (författare)
- CAS Ctr Excellence Nanosci, Natl Ctr Nanosci & Technol, CAS Key Lab Biomed Effects Nanomat & Nanosafety, Beijing, Peoples R China.;Univ Chinese Acad Sci, Beijing, Peoples R China.
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- Essand, Magnus (författare)
- Uppsala universitet,Klinisk immunologi,Science for Life Laboratory, SciLifeLab
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- Karlsson-Parra, Alex (författare)
- Immunicum AB, Stockholm, Sweden.
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- Yu, Di, 1985- (författare)
- Uppsala universitet,Klinisk immunologi,Science for Life Laboratory, SciLifeLab
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(creator_code:org_t)
- Informa UK Limited, 2022
- 2022
- Engelska.
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Ingår i: Oncoimmunology. - : Informa UK Limited. - 2162-4011 .- 2162-402X. ; 11:1
- Relaterad länk:
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https://doi.org/10.1...
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https://uu.diva-port... (primary) (Raw object)
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Immune checkpoint inhibitors (ICIs) have revolutionized the oncology field. However, a significant number of patients do not respond, at least partly due to the lack of preexisting anti-tumor T-cell immunity. Therefore, it is emergent to add an immune-priming step to improve efficacy. Here, we report a combined approach consisting of intratumoral administration of pro-inflammatory allogeneic dendritic cells (AlloDCs) and systemic treatment with alpha CTLA-4 that can drastically improve the anti-tumor efficacy compared to alpha CTLA-4 monotherapy. When evaluated in mice with large established CT-26 tumors, monotherapy with alpha CTLA-4 neither delayed tumor progression nor improved mice survival. However, combination treatment of AlloDCs and alpha CTLA-4 drastically improved the effectiveness, with 70% of mice being cured. This effect was T cell-dependent, and all survived mice rejected a subsequent tumor re-challenge. Further investigation revealed an immune-inflamed tumor microenvironment (TME) in the combination treatment group characterized by enhanced infiltration of activated antigen-presenting endogenous DCs and CD8(+) T cells with a tissue-resident memory (T-RM) phenotype (CD49a(+)CD103(+)). This correlated with elevated levels of tumor-specific CD39(+)CD103(+)CD8(+) T cells in the tumor and "tumor-matching" NKG2D(+)CD39(+)CX3CR1(+)CD8(+) T cells in peripheral blood. Moreover, splenocytes from mice in the combination treatment group secreted significantly higher IFN-gamma upon stimulation with the peptide from the endogenous CT-26 retroviral gp70 (model neoantigen), confirming the induction of a tumor-specific CD8(+) T-cell response. Taken together, these data indicate a strong anti-tumor synergy between AlloDCs and alpha CTLA-4 that warrant further clinical investigation with the corresponding human AlloDC product (ilixadencel) for patients receiving alpha CTLA-4 therapy.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Immunology in the medical area (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Nyckelord
- Ilixadencel
- pro-inflammatory allogeneic dendritic cells
- alpha CTLA-4 therapy
- tissue-residentCD8(+)T cells
- tumor-reactiveCD8(+) T cells
- tumor-specificCD8(+) T cells
- tumor-matching T cells
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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Till lärosätets databas
- Av författaren/redakt...
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Jin, Chuan, 1986 ...
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Ali, Arwa
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Iskantar, Alexan ...
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Fotaki, Grammati ...
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Wang, Hai
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Essand, Magnus
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Karlsson-Parra, ...
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Yu, Di, 1985-
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Oncoimmunology
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Uppsala universitet