Characterization of a human anti-tumoral NK cell population expanded after BCG treatment of leukocytes

Oncoimmunology
Eva M García-CuestaMar Valés-Gómez

Abstract

Immunotherapy, via intra-vesical instillations of BCG, is the therapy of choice for patients with high-risk non-muscle invasive bladder cancer. The subsequent recruitment of lymphocytes and myeloid cells, as well as the release of cytokines and chemokines, is believed to induce a local immune response that eliminates these tumors, but the detailed mechanisms of action of this therapy are not well understood. Here, we have studied the phenotype and function of the responding lymphocyte populations as well as the spectrum of cytokines and chemokines produced in an in vitro model of human peripheral blood mononuclear cells (PBMCs) co-cultured with BCG. Natural killer (NK) cell activation was a prominent feature of this immune response and we have studied the expansion of this lymphocyte population in detail. We show that, after BCG stimulation, CD56dim NK cells proliferate, upregulate CD56, but maintain the expression of CD16 and the ability to mediate ADCC. CD56bright NK cells also contribute to this expansion by increasing CD16 and KIR expression. These unconventional CD56bright cells efficiently degranulated against bladder cancer cells and the expansion of this population required the release of soluble factors by other immune...Continue Reading

References

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Citations

Aug 10, 2017·Frontiers in Immunology·Heleen H Van AckerViggo F Van Tendeloo
Dec 14, 2018·Oncoimmunology·Jonathan G PolLorenzo Galluzzi
Jul 6, 2019·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Nicola E AnnelsHardev S Pandha
Mar 13, 2021·Frontiers in Immunology·Gloria EstesoMar Valés-Gómez

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Methods Mentioned

BETA
flow cytometry

Software Mentioned

FlowJo
GraphPad Prism
Kaluza
Bio
Plex [UNK]
Prism

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