Profiling Blood Lymphocyte Interactions with Cancer Cells Uncovers the Innate Reactivity of Human γδ T Cells to Anaplastic Large Cell Lymphoma

Abstract

Quantifying the contacts that circulating lymphocytes have with cancer cells is useful, because their deficit favors malignancy progression. All normal lymphocytes contact, scan, and acquire membrane fragments (trogocytosis) from foreign cells for their immunosurveillance. So in this study, we used the in vitro trogocytosis of PKH67-stained cancer cell lines as a measure of their interactions with bulks of PBMC freshly isolated from healthy donors. Allogeneic PBMC mixed and coincubated in vitro for 1 h did not trogocytosis, whereas in the same conditions CD20+, CD4+, CD8+, γδ T, and CD16+ PBMC interacted strongly with the cancer cells. Although most unprimed lymphoid effectors of innate (NK) and adaptive (B and T) immunity from healthy donors spontaneously trogocytosed different tumoral cell lines, some carcinoma cell lines could escape them in the coculture. This also uncovered the strong interactions of circulating Vγ9/Vδ2+ central memory γδ T cells with anaplastic large cell lymphoma. These interaction profiles were stable upon time for healthy blood donors but were different with other tumors and blood donors. This profiling provides interaction signatures for the immunomonitoring of cancer.