γδ T cells lyse autologous and allogenic oesophageal tumours: involvement of heat-shock proteins in the tumour cell lysis

Abstract

T cells expressing gammadelta receptors were isolated from the peripheral blood of oesophageal cancer patients and analysed for their potential to lyse tumour targets. Immunophenotyping by flow cytometry showed that the dominant population of gammadelta T cells expressed the Vgamma9 and the Vdelta2 T cell receptor, and a minor population expressed the Vdelta1 receptor. Cytotoxicity assays revealed that activated gammadelta T cells lysed Daudi Burkitt's lymphoma and K562 cells. Lysis of autologous oesophageal tumours was higher than of allogenic tumours. Anti-hsp60 and anti-hsp70 mAb significantly inhibited the cytotoxicity of gammadelta T cells to both autologous and allogenic oesophageal tumours. Surface expression of hsp60 and hsp70 on oesophageal tumours and Daudi cells was demonstrated by flow cytometry. In conclusion, gammadelta T cells isolated from the peripheral blood of oesophageal cancer patients have the ability of kill oesophageal tumour cells. The lysis of tumour targets by the gammadelta T cells is brought about via recognition of heat-shock proteins expressed on the surface of tumour cells. gammadelta T cells isolated from the peripheral blood may have applications in adoptive immunotherapy of oesophageal cancer.

DNAX accessory molecule‐1 (CD226) promotes human hepatocellular carcinoma cell lysis by Vγ9Vδ2 T cells

“…The capacity of gd T cells to recognize human tumor cells in a nonrestricted MHC manner is well documented [3,4,7,9]. However, the requirements for recognition of malignant cells are not completely understood.…”

“…Immunological approaches using innate antitumor effector cells are currently being evaluated in clinical trials [2]. Vg9Vd2 T cells represent the major population of human peripheral blood gd T cells and display an in vitro non-MHCrestricted lytic activity against a broad panel of tumors including colon, kidney, liver, esophageal, small-lung cancers and myeloma [3][4][5][6][7][8][9]. The presence of tumor-infiltrating Vd2 1 T cells in tumorbearing livers of patients may support their potential role in tumor immunosurveillance of HCC [10].…”

Individual Vγ2-Jγ1.2+ T cells respond to both isopentenyl pyrophosphate and Daudi cell stimulation: generating tumor effectors with low molecular weight phosphoantigens

“…Human γδ T cells comprise 1-10% of circulating lymphocytes [5,7,13,34] and the major subset expresses the Vγ2Vδ2 TCR but not the lineage determinants CD4 or CD8 [2]. The Vγ2Vδ2 T cell population is largely effector memory [23] and is potently cytotoxic for the Daudi B cell lymphoma [30] and other tumor targets [10,21,26,39]. Because Vγ2Vδ2 T cells represent an abundant effector memory population that is cytotoxic for tumor cells, there is a growing interest in understanding these cells and exploiting their capabilities in the development of new immunotherapies against malignancies [27,41].…”

Lymphocytes Tγδ en cancérologie

“…Les lignées établies à partir de tumeurs solides sont également sensibles à la lyse in vitro par les cellules T Vγ9Vδ2. Cette reconnaissance a initialement été établie à partir de cellules de carcinomes oesophagiens [17] puis étendue à bien d'autres types histologiques de tumeur [7]. Des cellules T Vγ9Vδ2 clonées à partir de liquide d'ascite chez un patient atteint d'un carcinome colorectal sont capables de lyser des lignées allogéniques de carcinome colique sans affecter des fibroblastes coliques normaux [8].…”