title: Densely granulated murine NK cells eradicate large solid tumors.
abstract: Natural killer (NK) cells inhibit early stages of tumor formation, recurrence, and metastasis. Here, we show that NK cells can also eradicate large solid tumors. Eradication depended on the massive infiltration of proliferating NK cells due to interleukin 15 (IL-15) released and presented by the cancer cells in the tumor microenvironment. Infiltrating NK cells had the striking morphologic feature of being densely loaded with periodic acid-Schiff-positive, diastase-resistant granules, resembling uterine NK cells. Perforin-mediated killing by these densely granulated NK cells was essential for tumor eradication. Expression of the IL-15 receptor α on cancer cells was needed to efficiently induce granulated NK cells, and expression on host stromal cells was essential to prevent tumor relapse after near complete destruction. These results indicate that IL-15 released at the cancer site induces highly activated NK cells that lead to eradication of large solid tumors.
authors.affiliation: Committee on Immunology, Department of Pathology, The University of Chicago, Chicago, Illinois 60637, USA.
authors.forename: Rebecca B
authors.initials: RB
authors.lastname: Liu
authors.forename: Boris
authors.initials: B
authors.lastname: Engels
authors.forename: Ainhoa
authors.initials: A
authors.lastname: Arina
authors.forename: Karin
authors.initials: K
authors.lastname: Schreiber
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Hyjek
authors.forename: Andrea
authors.initials: A
authors.lastname: Schietinger
authors.forename: David C
authors.initials: DC
authors.lastname: Binder
authors.forename: Eric
authors.initials: E
authors.lastname: Butz
authors.forename: Thomas
authors.initials: T
authors.lastname: Krausz
authors.forename: Donald A
authors.initials: DA
authors.lastname: Rowley
authors.forename: Bana
authors.initials: B
authors.lastname: Jabri
authors.forename: Hans
authors.initials: H
authors.lastname: Schreiber
mesh_terms: D000818:Animals; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D007150:Immunohistochemistry; D002479:Inclusion Bodies; D019409:Interleukin-15 / Q000276:immunology* / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D009374:Neoplasms, Experimental / Q000276:immunology* / Q000378:metabolism; D059016:Tumor Microenvironment / Q000276:immunology*
chemical_list: D019409:Interleukin-15