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Multidimensional analyses of donor memory-like NK cells reveal new associations with response after adoptive immunotherapy for leukemia

Berrien-Elliot, M., Cashen, A.F., Cubitt, C.C.

NK cells are an emerging cancer cellular therapy and potent mediators of anti-tumor immunity. Cytokine-induced memory-like (ML) NK cellular therapy is safe and induces remissions in acute myeloid leukemia (AML) patients. However, the dynamic changes in phenotype that occur after NK cell transfer that impact patient outcomes remain unclear. Here, we report comprehensive multidimensional correlates from ML NK cell-treated AML patients using mass cytometry. These data identify a unique in vivo differentiated ML NK cell phenotype distinct from conventional NK cells. Moreover, the inhibitory receptor NKG2A is a dominant, transcriptionally-induced checkpoint important for ML, but not conventional NK cell responses to cancer. The frequency of CD8a+ donor NK cells is negatively associated with AML patient outcomes after ML NK therapy. Thus, elucidating the multidimensional dynamics of donor ML NK cells in vivo revealed critical factors important for clinical response, and new avenues to enhance NK cell therapeutics.

Citation

Berrien-Elliot, M., Cashen, A.F., Cubitt, C.C. "Multidimensional analyses of donor memory-like NK cells reveal new associations with response after adoptive immunotherapy for leukemia" Cancer Discovery (2020): DOI: 10.1158/2159-8290.CD-20-0312