Requirement for innate immunity and CD90    NK1.1    lymphocytes to treat established XXXX with chemo-immunotherapy.

@entity2047 @entity5 @entity22837 @entity19 @entity786 @entity5350 @entity14434 @entity320
We sought to define cellular immune mechanisms of synergy between @entity5 -antigen-targeted monoclonal antibodies and chemotherapy. Established B16 @entity320 in @entity19 was treated with cytotoxic doses of @entity786 in combination with an antibody targeting @entity22837 (aTRP1), a native @entity320 differentiation antigen. We find that Fcy receptors are required for efficacy, showing that antitumor activity of combination therapy is immune mediated. @entity5350 (-/-) @entity19 deficient in adaptive immunity are able to clear @entity5 , and thus innate immunity is sufficient for efficacy. Furthermore, previously treated wild-type @entity19 are not significantly protected against @entity5 reinduction, as compared with @entity19 inoculated with irradiated B16 alone, consistent with a primarily innate immune mechanism of action of chemo-immunotherapy. In contrast, @entity19 @entity14434 (NK) lymphocytes and nonclassical innate lymphocytes (ILC) due to deletion of the @entity2047 receptor common gamma chain @entity2047 yc(-/-)) are refractory to chemo-immunotherapy. Classical NK lymphocytes are not critical for treatment, as depletion of NK1.1    cells does not impair antitumor effect. Depletion of CD90   NK1.1    lymphocytes, however, both diminishes therapeutic benefit and decreases accumulation of macrophages within the @entity5 . @entity5 clearance during combination chemo-immunotherapy with monoclonal antibodies against native antigen is mediated by the innate immune system. We highlight a novel potential role for CD90   NK1.1    ILCs in chemo-immunotherapy.
