Aminobisphosphonates prevent the inhibitory effects exerted by lymph node stromal cells on anti-tumor V  2 T lymphocytes in non-Hodgkin lymphomas

Musso, Alessandra; Catellani, Silvia; Canevali, Paolo; Tavella, Sara; Venè, Roberta; Boero, Silvia; Pierri, Ivana; Gobbi, Marco; Kunkl, Annalisa; Ravetti, Jean Louis; Zocchi, Maria Raffaella; Poggi, Alessandro

doi:10.3324/haematol.2013.097311

Cited by 27 publications

(46 citation statements)

References 44 publications

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“…The phenotype of such lymphocyte population, that was mostly naive (co-expression of CD45RA and CD27) at the beginning of the co-culture, was that of EM cells, based on the lack of CD45RA and CD27 expression. 35,36 Furthermore, Zol could sensitize CRC cell lines, including those that poorly triggered gd T cell growth, to become targets for the cytotoxic effect exerted by activated gd T lymphocytes. Given the heterogeneity of the stimulating ability displayed by the various CRC cell lines, we asked whether this was due to a different sensitivity of farnesyl diphosphate synthase to Zol, as reported.…”

Section: Discussionmentioning

confidence: 99%

“…In particular, we focused on the distinction of naive (N), bearing CD27 and CD45RA molecules, central memory (CM), showing only CD27, EM that are double negative, and terminal-differentiated memory cells (TEMRA) that are surface positive CD45RA. 35,36 We found that upon Zol treatment, LS180 cells could drive the expansion of gdT cells showing the characteristics of EM T lymphocytes (i.e., absence of CD27 and CD45RA) ( Fig. 2A, two representative experiments; Fig.…”

Section: Crc Exposed To Zol Stimulate the Expansion Of Vd2 T Cells Wimentioning

confidence: 99%

“…Monocytes (Mo) were isolated from PBMC using the anti-CD14 mAb (MEM18, IgG1, Exbio, Prague, CZ) and EasySep custom Kit (StemCell Technologies, Inc.) according to manufacturer's instructions, with recovery of > 97% CD14 positive cells. 36 The human CRC cell lines HT29, HCT15, HCT116, SW48, SW480, SW620, Colo741, Colo205, Colo320, CaCo2, LS180, WiDr, LoVo and DLD1 were obtained from the Biological Bank and Cell Factory of the IRCCS AOU San Martino IST (Genoa, Italy) and maintained in RPMI 1640 medium supplemented with 10% FCS and 1% L-glutamine (Gibco). T cells were cultured in RPMI 1640 complete medium with or without irradiated CRC cells or TAF, or CRC15-045 cell line, at a ratio of 1:10, or Mo (Mo:T ratios from 1:10 to 1:80), untreated or exposed for 24 h to zoledronic acid (Zol 5 mM, kindly provided as sodium salt by Novartis Pharma, Basel, Switzerland, MTA 37318); the dose was selected on the basis of the effectiveness on gd T cells proliferation from PBMCs cultures and absence of toxic effects according to the literature and our previous data.…”

Section: Isolation Of T Cells and Monocytes And Co-culturesmentioning

confidence: 99%

“…36 For the identification of gd T cell subpopulations, we used the anti-gd mAb BB3 (IgG1). 36 BTN3A1 expression was checked with the anti-CD277 mAb (clone 20.1, IgG1, Affimetrix eBioscience, Hatfield, UK).…”

Section: Immunofluorescence and Cytofluorimetric Analysesmentioning

confidence: 99%

“…Maximum and spontaneous release were calculated as described. 36 cDNA reverse transcription and quantitative real-time PCR (Q-RT-PCR) RNA was extracted either from cultured CRC cell lines or CRC tissue samples or cell suspensions. Paraffin-embedded sections (8-mm thick) of the CRC patients were fixed on PEN membrane glass slides (MDS Analytical Technologies GmbH, Ismaning, Germany), dried at room temperature under a chemical safety hood for 5 min, dipped in xylene for 10 min twice for each sample, followed by a 3-step immersion in 100%/95%/75% ethanol solution.…”

Section: Cytotoxicity Assaymentioning

confidence: 99%

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Zoledronate can induce colorectal cancer microenvironment expressing BTN3A1 to stimulate effector γδ T cells with antitumor activity

et al. 2017

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Amino-bis-phosphonates (N-BPs) such as zoledronate (Zol) have been used in anticancer clinical trials due to their ability to upregulate pyrophosphate accumulation promoting antitumor Vg9Vd2 T cells. The butyrophilin 3A (BTN3A, CD277) family, mainly the BTN3A1 isoform, has emerged as an important structure contributing to Vg9Vd2 T cells stimulation. It has been demonstrated that the B30.2 domain of BTN3A1 can bind phosphoantigens (PAg) and drive the activation of Vg9Vd2 T cells through conformational changes of the extracellular domains. Moreover, BTN3A1 binding to the cytoskeleton, and its consequent membrane stabilization, is crucial to stimulate the PAg-induced tumor cell reactivity by human Vg9Vd2 T cells. Aim of this study was to investigate the relevance of BTN3A1 in N-BPs-induced antitumor response in colorectal cancer (CRC) and the cell types involved in the tumor microenvironment.In this paper, we show that (i) CRC, exposed to Zol, stimulates the expansion of Vd2 T lymphocytes with effector memory phenotype and antitumor cytotoxic activity, besides sensitizing cancer cells to gd T cellmediated cytotoxicity; (ii) this effect is partially related to BTN3A1 expression and in particular with its cellular re-distribution in the membrane and cytoskeleton-associated fraction; (iii) BTN3A1 is detected in CRC at the tumor site, both on epithelial cells and on tumor-associated fibroblasts (TAF), close to areas infiltrated by Vd2 T lymphocytes; (iv) Zol is effective in stimulating antitumor effector Vd2 T cells from exvivo CRC cell suspensions; and (v) both CRC cells and TAF can be primed by Zol to trigger Vd2 T cells.

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Section: Discussionmentioning

confidence: 99%

Section: Crc Exposed To Zol Stimulate the Expansion Of Vd2 T Cells Wimentioning

confidence: 99%

Section: Isolation Of T Cells and Monocytes And Co-culturesmentioning

confidence: 99%

Section: Immunofluorescence and Cytofluorimetric Analysesmentioning

confidence: 99%

Section: Cytotoxicity Assaymentioning

confidence: 99%

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Zoledronate can induce colorectal cancer microenvironment expressing BTN3A1 to stimulate effector γδ T cells with antitumor activity

et al. 2017

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Design and Synthesis of Ionic Liquid‐Based Matrix Metalloproteinase Inhibitors (MMPIs): A Simple Approach to Increase Hydrophilicity and to Develop MMPI‐Coated Gold Nanoparticles

et al. 2019

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Selective and potent matrix metalloproteinase 12 (MMP‐12) inhibitors endowed with improved hydrophilicity are highly sought for potential use in the treatment of lung and cardiovascular diseases. In the present paper, we modified the structure of a nanomolar MMP‐12 inhibitor by incorporating an ionic liquid (IL) moiety to improve aqueous solubility. Four biologically active salts were obtained by linking the sulfonamide moiety of the MMP‐12 inhibitor to imidazolium‐, pyrrolidinium‐, piperidinium‐, and DABCO‐based ILs. The imidazolium‐based bioactive salt was tested on human recombinant MMPs and on monocyte‐derived dendritic cells, showing activity similar to that of the parent compound, but improved water solubility. The imidazolium‐based bioactive salt was then used to prepare electrostatically stabilized MMP inhibitor‐coated gold nanoparticles (AuNPs) able to selectively bind MMP‐12. These AuNPs were used to study subcellular localization of MMP‐12 in monocyte‐derived dendritic cells by transmission electron microscopy analysis.

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Preclinical platforms to study therapeutic efficacy of human γδ T cells

Wang

Huang

et al. 2022

Clinical & Translational Med

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Aminobisphosphonates prevent the inhibitory effects exerted by lymph node stromal cells on anti-tumor V 2 T lymphocytes in non-Hodgkin lymphomas

Cited by 27 publications

References 44 publications

Zoledronate can induce colorectal cancer microenvironment expressing BTN3A1 to stimulate effector γδ T cells with antitumor activity

Zoledronate can induce colorectal cancer microenvironment expressing BTN3A1 to stimulate effector γδ T cells with antitumor activity

Design and Synthesis of Ionic Liquid‐Based Matrix Metalloproteinase Inhibitors (MMPIs): A Simple Approach to Increase Hydrophilicity and to Develop MMPI‐Coated Gold Nanoparticles

Preclinical platforms to study therapeutic efficacy of human γδ T cells

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