Data from Donor Lymphocyte–Derived Natural Killer Cells Control MHC Class I–Negative Melanoma

• DOI: 10.1158/2326-6066.c.6550371.v1
• Publication Date: 2023-04-04T19:39:33Z
• Authors: Nana Dang; Yuan Lin; Mark Waer; Ben Sprangers
• Keywords: NKG2D; Tumor-infiltrating lymphocytes

<div>Abstract<p>Natural killer (NK) cells provide a natural defense against MHC-I–negative tumors, such as melanoma. Donor lymphocyte infusion (DLI) containing NK cells, form of adoptive immunotherapy used after allogenic bone marrow transplantation (allo-BMT), promotes antitumor immune responses but is often associated with life-threatening complications graft-versus-host disease (GvHD). Here, we showed that without prior allo-BMT, DLI provoked melanoma control the infiltration and persistence transferred cells. This allograft acceptance did not correlate an increase GvHD; instead it correlated expansion activation tumor-infiltrating expressed cytotoxic molecules (e.g., IFNγ granzyme B) maturation signatures CD11b<sup>hi</sup>CD27<sup>lo</sup> KLRG<sup>hi</sup>/CD43<sup>hi</sup>). The development beneficial origin required host CD4<sup>+</sup> T-cell help in part by producing IL2, well limiting regulatory T (Treg). IL2 blockade impaired NK-dependent control, which could be rescued administration beyond help. Our findings linked acceptance–CD4<sup>+</sup> crosstalk to need allo-BMT. We thereby helped define may serve effective therapeutic targets for controlling melanoma.</p></div>