Constant P, Davodeau F, Peyrat MA, Poquet Y, Puzo G, Bonneville M, et al. Stimulation of human gamma delta T cells by nonpeptidic mycobacterial ligands. Science. 1994;264:267–70. https://doi.org/10.1126/science.8146660.

Article  ADS  PubMed  CAS  Google Scholar 

Xu Y, Xiang Z, Alnaggar M, Kouakanou L, Li J, He J, et al. Allogeneic Vγ9Vδ2 T-cell immunotherapy exhibits promising clinical safety and prolongs the survival of patients with late-stage lung or liver cancer. Cell Mol Immunol. 2021;18:427–39. https://doi.org/10.1038/s41423-020-0515-7.

Article  PubMed  CAS  Google Scholar 

Rhodes DA, Reith W, Trowsdale J. Regulation of Immunity by Butyrophilins. Annu Rev Immunol. 2016;34:151–72. https://doi.org/10.1146/annurev-immunol-041015-055435.

Article  PubMed  CAS  Google Scholar 

Rigau M, Ostrouska S, Fulford TS, Johnson DN, Woods K, Ruan Z, et al. Butyrophilin 2A1 is essential for phosphoantigen reactivity by gammadelta T cells. Science. 2020;367:eaay5516 https://doi.org/10.1126/science.aay5516.

Article  PubMed  CAS  Google Scholar 

Karunakaran MM, Willcox CR, Salim M, Paletta D, Fichtner AS, Noll A, et al. Butyrophilin-2A1 Directly Binds Germline-Encoded Regions of the Vgamma9Vdelta2 TCR and Is Essential for Phosphoantigen Sensing. Immunity. 2020;52:487–498 e486. https://doi.org/10.1016/j.immuni.2020.02.014.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Cano CE, Pasero C, De Gassart A, Kerneur C, Gabriac M, Fullana M, et al. BTN2A1, an immune checkpoint targeting Vgamma9Vdelta2 T cell cytotoxicity against malignant cells. Cell Rep. 2021;36:109359 https://doi.org/10.1016/j.celrep.2021.109359.

Article  PubMed  CAS  Google Scholar 

Vyborova A, Beringer DX, Fasci D, Karaiskaki F, van Diest E, Kramer L, et al. gamma9delta2T cell diversity and the receptor interface with tumor cells. J Clin Invest. 2020;130:4637–51. https://doi.org/10.1172/JCI132489.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Willcox CR, Vantourout P, Salim M, Zlatareva I, Melandri D, Zanardo L, et al. Butyrophilin-like 3 Directly Binds a Human Vgamma4(+) T Cell Receptor Using a Modality Distinct from Clonally-Restricted Antigen. Immunity. 2019;51:813–825 e814. https://doi.org/10.1016/j.immuni.2019.09.006.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Herrmann T, Karunakaran MM, Fichtner AS. A glance over the fence: Using phylogeny and species comparison for a better understanding of antigen recognition by human gammadelta T-cells. Immunol Rev. 2020;298:218–36. https://doi.org/10.1111/imr.12919.

Article  PubMed  CAS  Google Scholar 

Sandstrom A, Peigne CM, Leger A, Crooks JE, Konczak F, Gesnel MC, et al. The intracellular B30.2 domain of butyrophilin 3A1 binds phosphoantigens to mediate activation of human Vgamma9Vdelta2 T cells. Immunity. 2014;40:490–500. https://doi.org/10.1016/j.immuni.2014.03.003.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Hsiao CC, Nguyen K, Jin Y, Vinogradova O, Wiemer AJ. Ligand-induced interactions between butyrophilin 2A1 and 3A1 internal domains in the HMBPP receptor complex. Cell Chem Biol. 2022;29:985–995.e985. https://doi.org/10.1016/j.chembiol.2022.01.004.

Article  PubMed  CAS  Google Scholar 

Laplagne C, Meddour S, Figarol S, Michelas M, Calvayrac O, Favre G, et al. Vgamma9Vdelta2 T Cells Activation Through Phosphoantigens Can Be Impaired by a RHOB Rerouting in Lung Cancer. Front Immunol. 2020;11:1396 https://doi.org/10.3389/fimmu.2020.01396.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Wada I, Matsushita H, Noji S, Mori K, Yamashita H, Nomura S, et al. Intraperitoneal injection of in vitro expanded Vgamma9Vdelta2 T cells together with zoledronate for the treatment of malignant ascites due to gastric cancer. Cancer Med. 2014;3:362–75. https://doi.org/10.1002/cam4.196.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Benelli R, Costa D, Salvini L, Tardito S, Tosetti F, Villa F, et al. Targeting of colorectal cancer organoids with zoledronic acid conjugated to the anti-EGFR antibody cetuximab. J Immunother Cancer. 2022;10:e005660 https://doi.org/10.1136/jitc-2022-005660.

Article  PubMed  PubMed Central  Google Scholar 

Ravens S, Schultze-Florey C, Raha S, Sandrock I, Drenker M, Oberdorfer L, et al. Human gammadelta T cells are quickly reconstituted after stem-cell transplantation and show adaptive clonal expansion in response to viral infection. Nat Immunol. 2017;18:393–401. https://doi.org/10.1038/ni.3686.

Article  PubMed  CAS  Google Scholar 

Gentles AJ, Newman AM, Liu CL, Bratman SV, Feng W, Kim D, et al. The prognostic landscape of genes and infiltrating immune cells across human cancers. Nat Med. 2015;21:938–45. https://doi.org/10.1038/nm.3909.

Article  PubMed  PubMed Central  CAS  Google Scholar 

De Gassart A, Le KS, Brune P, Agaugue S, Sims J, Goubard A, et al. Development of ICT01, a first-in-class, anti-BTN3A antibody for activating Vgamma9Vdelta2 T cell-mediated antitumor immune response. Sci Transl Med. 2021;13:eabj0835 https://doi.org/10.1126/scitranslmed.abj0835.

Article  PubMed  CAS  Google Scholar 

Zhu S, Cao Z, Liu Z, He Y, Wang Y, Yuan P, et al. Guide RNAs with embedded barcodes boost CRISPR-pooled screens. Genome Biol. 2019;20:20 https://doi.org/10.1186/s13059-019-1628-0.

Article  PubMed  PubMed Central  Google Scholar 

Bui TM, Wiesolek HL, Sumagin R. ICAM-1: A master regulator of cellular responses in inflammation, injury resolution, and tumorigenesis. J Leukoc Biol. 2020;108:787–99. https://doi.org/10.1002/jlb.2mr0220-549r.

Article  PubMed  CAS  Google Scholar 

Uchida R, Ashihara E, Sato K, Kimura S, Kuroda J, Takeuchi M, et al. Gamma delta T cells kill myeloma cells by sensing mevalonate metabolites and ICAM-1 molecules on cell surface. Biochem Biophys Res Commun. 2007;354:613–8. https://doi.org/10.1016/j.bbrc.2007.01.031.

Article  PubMed  CAS  Google Scholar 

Patel SJ, Sanjana NE, Kishton RJ, Eidizadeh A, Vodnala SK, Cam M, et al. Identification of essential genes for cancer immunotherapy. Nature. 2017;548:537–42. https://doi.org/10.1038/nature23477.

Article  ADS  PubMed  PubMed Central  CAS  Google Scholar 

Cazzetta V, Bruni E, Terzoli S, Carenza C, Franzese S, Piazza R, et al. NKG2A expression identifies a subset of human Vδ2 T cells exerting the highest antitumor effector functions. Cell Rep. 2021;37:109871 https://doi.org/10.1016/j.celrep.2021.109871.

Article  PubMed  CAS  Google Scholar 

Reith W, Mach B. The bare lymphocyte syndrome and the regulation of MHC expression. Annu Rev Immunol. 2001;19:331–73. https://doi.org/10.1146/annurev.immunol.19.1.331.

Article  PubMed  CAS  Google Scholar 

Reith W, Siegrist CA, Durand B, Barras E, Mach B. Function of major histocompatibility complex class II promoters requires cooperative binding between factors RFX and NF-Y. Proc Natl Acad Sci USA. 1994;91:554–8. https://doi.org/10.1073/pnas.91.2.554.

Article  ADS  PubMed  PubMed Central  CAS  Google Scholar 

Masternak K, Barras E, Zufferey M, Conrad B, Corthals G, Aebersold R, et al. A gene encoding a novel RFX-associated transactivator is mutated in the majority of MHC class II deficiency patients. Nat Genet. 1998;20:273–7. https://doi.org/10.1038/3081.

Article  PubMed  CAS  Google Scholar 

Dang AT, Strietz J, Zenobi A, Khameneh HJ, Brandl SM, Lozza L, et al. NLRC5 promotes transcription of BTN3A1-3 genes and Vgamma9Vdelta2 T cell-mediated killing. iScience. 2021;24:101900 https://doi.org/10.1016/j.isci.2020.101900.

Article  ADS  PubMed  CAS  Google Scholar 

Stephan A, Wermann M, von Bohlen A, Koch B, Cynis H, Demuth HU, et al. Mammalian glutaminyl cyclases and their isoenzymes have identical enzymatic characteristics. FEBS J. 2009;276:6522–36. https://doi.org/10.1111/j.1742-4658.2009.07337.x.

Article  PubMed  CAS  Google Scholar 

Logtenberg MEW, Jansen JHM, Raaben M, Toebes M, Franke K, Brandsma AM, et al. Glutaminyl cyclase is an enzymatic modifier of the CD47- SIRPalpha axis and a target for cancer immunotherapy. Nat Med. 2019;25:612–9. https://doi.org/10.1038/s41591-019-0356-z.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Thompson K, Rogers MJ, Coxon FP, Crockett JC. Cytosolic entry of bisphosphonate drugs requires acidification of vesicles after fluid-phase endocytosis. Mol Pharm. 2006;69:1624–32. https://doi.org/10.1124/mol.105.020776.

Article  CAS  Google Scholar 

Yu Z, Surface LE, Park CY, Horlbeck MA, Wyant GA, Abu-Remaileh M, et al. Identification of a transporter complex responsible for the cytosolic entry of nitrogen-containing bisphosphonates. Elife. 2018;7:e36620 https://doi.org/10.7554/eLife.36620.

Article  PubMed  PubMed Central  Google Scholar 

McGilvray PT, Anghel SA, Sundaram A, Zhong F, Trnka MJ, Fuller JR, et al. An ER translocon for multi-pass membrane protein biogenesis. Elife. 2020;9:e56889 https://doi.org/10.7554/eLife.56889.