Myeloid molecular characteristics of human γδ T cells support their acquisition of tumor antigen-presenting capacity
Open accessAbstract
Human T cells expressing γδ T cell receptor have a potential to show antigen-presenting cell-like phenotype and function upon their activation. However, the mechanisms that underlie the alterations in human γδ T cells remain largely unclear. In this study, we have investigated the molecular characteristics of human γδ T cells related to their acquisition of antigen-presenting capacity in comparison with activated αβ T cells. We found that activated γδ but not αβ T cells upregulated cell surface expression of a scavenger receptor, CD36, which seemed to be mediated by signaling through mitogen-activated protein kinase and/or NF-κB pathways. Confocal microscopical analysis revealed that activated γδ T cells can phagocytose protein antigens. Activated γδ T cells could induce tumor antigen-specific CD8(+) T cells using both apoptotic and live tumor cells as antigen resources. Furthermore, we detected that C/EBPα, a critical transcription factor for the development of myeloid-lineage cells, is expressed much higher in γδ T cells than in αβ T cells. These results unveiled the molecular mechanisms for the elicitation of antigen-presenting functions in γδ T cells and would also help designing new approaches for γδ T cell-mediated human cancer immunotherapy.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
PU.1 upregulates costimulatory receptors such as CD80 and CD86.
“For upregulating costimulatory receptors, such as CD80 and CD86, PU.1 (Purine Rich Box-1) is a crucial key factor that also controls antigen presentation and the induction of type-I interferon [10].”
From Ectopic PU.1 Expression Provides Chimeric Antigen Receptor (CAR) T Cells with Innate Cell Capacities Including IFN-β Release (2024) · cites this paper as [24]
The transcription-factor comparison (p. 6) measures PU.1 expression but does not test whether PU.1 upregulates CD80 or CD86. The signaling-pathway results (p. 5) examine MAPK and NFκB instead; the searched passages also do not link PU.1 to type-I interferon induction. (LLM, conf=0.74)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
No references could be resolved yet.
Research works printed but not linked: 20
- [1]1. Kabelitz D, Wesch D, Pitters E, Zöller M (2004) Potential of human gammadelta T lymphocytes for immunotherapy of cancer. Int J Cancer 112(5):727-732
- [3]3. Bennouna J, Bompas E, Neidhardt EM, Rolland F, Philip I, Galéa C, Salot S, Saiagh S, Audrain M, Rimbert M, Lafaye-de Micheaux S, Tiollier J, Négrier S (2008) Phase-I study of Innacell gammadelta, an autologous cell-therapy product highly enriched in gamma9delta2 T lymphocytes, in combination with IL-2, in patients with metastatic renal cell carcinoma. Cancer Immunol Immunother 57(11):1599-1609
- [4]4. Kobayashi H, Tanaka Y, Yagi J, Minato N, Tanabe K (2011) Phase I/II study of adoptive transfer of γδ T cells in combination with zoledronic acid and IL-2 to patients with advanced renal cell carcinoma. Cancer Immunol Immunother 60(8):1075-1084
- [7]7. Wada I, Matsushita H, Noji S, Mori K, Yamashita H, Nomura S, Shimizu N, Seto Y, Kakimi K (2014) Intraperitoneal injection of in vitro expanded V γ 9V δ 2 T cells together with zoledronate for - the treatment of malignant ascites due to gastric cancer. Cancer Med 3(2):362-375
- [10]10. Wilhelm M, Kunzmann V, Eckstein S, Reimer P, Weissinger F, Ruediger T, Tony HP (2003) Gammadelta T cells for immune therapy of patients with lymphoid malignancies. Blood 102(1):200-206
- [12]12. Brandes M, Willimann K, Moser B (2005) Professional antigenpresentation function by human gammadelta T cells. Science 309(5732):264-268
- [13]13. Wu Y, Wu W, Wong WM, Ward E, Thrasher AJ, Goldblatt D, Osman M, Digard P, Canaday DH, Gustafsson K (2009) Human gamma delta T cells: a lymphoid lineage cell capable of professional phagocytosis. J Immunol 183(9):5622-5629
- [16]16. Brandes M, Willimann K, Bioley G, Lévy N, Eberl M, Luo M, Tampé R, Lévy F, Romero P, Moser B (2009) Cross-presenting human γδ T cells induce robust CD8 + αβ T cell responses. Proc Natl Acad Sci USA 106(7):2307-2312
- [17]17. Himoudi N, Morgenstern DA, Yan M, Vernay B, Saraiva L, Wu Y, Cohen CJ, Gustafsson K, Anderson J (2012) Human γδ T lymphocytes are licensed for professional antigen presentation by interaction with opsonized target cells. J Immunol 188(4):1708-1716
- [18]18. Umeshappa CS, Huang H, Xie Y, Wei Y, Mulligan SJ, Deng Y, Xiang J (2009) CD4 + Th-APC with acquired peptide/MHC class - I and II complexes stimulate type 1 helper CD4 + and central memory CD8 + T cell responses. J Immunol 182(1):193-206
- [19]19. Hao S, Yuan J, Xiang J (2007) Nonspecific CD4 + T cells with uptake of antigen-specific dendritic cell-released exosomes stimulate antigen-specific CD8 + CTL responses and long-term T cell memory. J Leukoc Biol 82(4):829-838
- [20]20. Hollis A, Speri B, Graber M, Berg T (2012) The natural product betulinic acid inhibits C/EBP family transcription factors. ChemBioChem 13(2):302-307
- [21]21. Albert ML, Pearce SF, Francisco LM, Sauter B, Roy P, Silverstein RL, Bhardwaj N (1998) Immature dendritic cells phagocytose apoptotic cells via alphavbeta5 and CD36, and cross-present antigens to cytotoxic T lymphocytes. J Exp Med 188(7):1359-1368
- [22]22. Greenberg ME, Sun M, Zhang R, Febbraio M, Silverstein R, Hazen SL (2006) Oxidized phosphatidylserine-CD36 interactions play an essential role in macrophage-dependent phagocytosis of apoptotic cells. J Exp Med 203(12):2613-2625
- [23]23. Ardeshna KM, Pizzey AR, Devereux S, Khwaja A (2000) The PI3 kinase, p38 SAP kinase, and NF-kappaB signal transduction pathways are involved in the survival and maturation of lipopolysaccharide-stimulated human monocyte-derived dendritic cells. Blood 96(3):1039-1046
- [24]24. Yoshimura S, Bondeson J, Foxwell BM, Brennan FM, Feldmann M (2001) Effective antigen presentation by dendritic cells is NFkappaB dependent: coordinate regulation of MHC, co-stimulatory molecules and cytokines. Int Immunol 13(5):675-683
- [25]25. Lubick K, Jutila MA (2006) LTA recognition by bovine gammadelta T cells involves CD36. J Leukoc Biol 79(6):1268-1270
- [26]26. Ross SE, Radomska HS, Wu B, Zhang P, Winnay JN, Bajnok L, Wright WS, Schaufele F, Tenen DG, MacDougald OA (2004) Phosphorylation of C/EBPalpha inhibits granulopoiesis. Mol Cell Biol 24(2):675-686
- [27]27. Qiao L, Zou C, Shao P, Schaack J, Johnson PF, Shao J (2008) Transcriptional regulation of fatty acid translocase/CD36 expression by CCAAT/enhancer-binding protein alpha. J Biol Chem 283(14):8788-8795
- [28]28. Meuter S, Eberl M, Moser B (2010) Prolonged antigen survival and cytosolic export in cross-presenting human gammadelta T cells. Proc Natl Acad Sci USA 107(19):8730-8735 <!-- image -->
Cited by
Sorted by citations
Harrer, D. C., Eder, M., Barden, M., Pan, H., Herr, W., & Abken, H. (2024) · Cancers · doi:10.3390/cancers16152737 · Cited by 1 · see citing works
- Authors
- Muto, M., Baghdadi, M., Maekawa, R., Wada, H., & Seino, K.-I.
- Affiliations
- Hokkaido University (JP)
- Medinet Co., Ltd. (Japan) (JP)
- Corresponding author
- Seino, Ken-ichiro
- Venue
- Cancer Immunology, Immunotherapy
- Published
- 2015-04-24
- Volume
- 64
- Issue
- 8
- Pages
- 941-949
- ISSN
- 0340-7004 (ISSN-L)
- 1432-0851
- PMC
- PMC11028926
- OpenAlex
- W2084343347
- Cited by
- 50
- References
- 0
- Citations by year
- 2026: 2 · 2025: 7 · 2024: 7 · 2023: 3 · 2022: 5 · 2021: 8 · 2020: 6 · 2019: 3 · 2018: 4 · 2017: 2 · 2016: 3
- FWCI
- 1.48
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Cancer Immunology Immunotherapy (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Institutional Repositories DataBase (IRDB) (submittedVersion)
- Hokkaido University Collection of Scholarly and Academic Papers (Hokkaido University) (submittedVersion)
- Funders
- Japan Society for the Promotion of Science (26640066)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Keywords
- γδ T cells, CD36, scavenger receptors, mitogen-activated protein kinase, NF-κB signaling, phagocytosis, tumor antigen presentation, CD8+ T cell activation, C/EBPα, myeloid lineage, alpha beta T cells
- MeSH terms
- Antigens, Neoplasm, Cell Differentiation, Cytotoxicity, Immunologic, Heterocyclic Compounds, 3-Ring, Humans, Imidazoles, Immunotherapy, Lymphocyte Activation, Neoplasms, Phagocytosis, Pyridines, T-Lymphocytes, Signal Transduction, Up-Regulation, NF-kappa B, Receptors, Antigen, T-Cell, gamma-delta, Antigen Presentation, CD8-Positive T-Lymphocytes, CD36 Antigens, Cell Lineage, Myeloid Cells, CCAAT-Enhancer-Binding Proteins, Cell Line, Tumor, p38 Mitogen-Activated Protein Kinases, MART-1 Antigen
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
