Journal article
PD-1 checkpoint blockade enhances adoptive immunotherapy by human V gamma 2V delta 2 T cells against human prostate cancer
Oncoimmunology, Vol.10(1), e1989789
01/01/2021
DOI: 10.1080/2162402X.2021.1989789
PMCID: PMC8547840
PMID: 34712512
Abstract
Human V gamma 2V delta 2 (also termed V gamma 9V delta 2) T cells play important roles in microbial and tumor immunity by monitoring foreign- and self-prenyl pyrophosphate metabolites in isoprenoid biosynthesis. Accumulation of isoprenoid metabolites after bisphosphonate treatment allows V gamma 2V delta 2 T cells to recognize and kill tumors independently of their MHC expression or burden of non-synonymous mutations. Clinical trials with more than 400 patients show that adoptive immunotherapy with V gamma 2V delta 2 T cells has few side effects but has resulted in only a few partial and complete remissions. Here, we have tested V gamma 2V delta 2 T cells for expression of inhibitory receptors and determined whether adding PD-1 checkpoint blockade to adoptively transferred V gamma 2V delta 2 T cells enhances immunity to human PC-3 prostate tumors in an NSG mouse model. We find that V gamma 2V delta 2 T cells express PD-1, CTLA-4, LAG-3, and TIM-3 inhibitory receptors during the 14-day ex vivo expansion period, and PD-1, LAG-3, and TIM-3 upon subsequent stimulation by pamidronate-treated tumor cells. Expression of PD-L1 on PC-3 prostate cancer cells was increased by co-culture with activated V gamma 2V delta 2 T cells. Importantly, anti-PD-1 mAb treatment enhanced V gamma 2V delta 2 T cell immunity to PC-3 tumors in immunodeficient NSG mice, reducing tumor volume nearly to zero after 5 weeks. These results demonstrate that PD-1 checkpoint blockade can enhance the effectiveness of adoptive immunotherapy with human gamma delta T cells in treating prostate tumors in a preclinical model.
Details
- Title: Subtitle
- PD-1 checkpoint blockade enhances adoptive immunotherapy by human V gamma 2V delta 2 T cells against human prostate cancer
- Creators
- Mohanad H. Nada - United States Department of Veterans AffairsHong Wang - University of Iowa, Internal MedicineAuter J. Hussein - United States Department of Veterans AffairsYoshimasa Tanaka - Nagasaki UniversityCraig T. Morita - University of Iowa, Internal Medicine
- Resource Type
- Journal article
- Publication Details
- Oncoimmunology, Vol.10(1), e1989789
- Publisher
- Taylor & Francis
- DOI
- 10.1080/2162402X.2021.1989789
- PMID
- 34712512
- PMCID
- PMC8547840
- ISSN
- 2162-402X
- eISSN
- 2162-402X
- Number of pages
- 17
- Grant note
- Higher Committee for Education Development in Iraq 16K08844 / Ministry of Education, Science, Culture, Sports, and Technology of Japan (MEXT); Ministry of Education, Culture, Sports, Science and Technology, Japan (MEXT) Japan Agency for Medical Research and Development; Japan Agency for Medical Research and Development (AMED) 2I01 BX000972-05 / Department of Veterans Affairs (Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development Grant); US Department of Veterans Affairs P30 CA086862 / National Institutes of Health, National Cancer Institute; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI)
- Language
- English
- Date published
- 01/01/2021
- Academic Unit
- Immunology; Internal Medicine
- Record Identifier
- 9984359904602771
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