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NK activation is dependent on the balance of inhibitory and excitatory signals transmitted by NK receptors, including Fc-gamma receptors (FC\u03b3Rs) and killer immunoglobulin-like receptors (KIRs) along with their KIR-ligands. The repertoire of KIRs\/KIR-ligands an individual inherits and the single-nucleotide polymorphisms (SNPs) of FC\u03b3Rs can influence NK function and affect responses to immunotherapies. In this retrospective analysis of the single-arm PIVOT-02 trial, 200 patients with advanced solid tumors were genotyped for KIR\/KIR-ligand gene status and FC\u03b3R SNP status and evaluated for associations with clinical outcome. Patients with inhibitory KIR2DL2 and its ligand (HLA-C1) observed significantly greater tumor shrinkage (TS, median change \u221213.0 vs. 0%) and increased PFS (5.5 vs. 3.3\u00a0months) and a trend toward improved OR (31.2 vs. 19.5%) compared to patients with the complementary genotype. Furthermore, patients with KIR2DL2 and its ligand together with inhibitory KIR3DL1 and its ligand (HLA-Bw4) had improved OR (36.5 vs. 19.6%), greater TS (median change \u221216.1 vs. 0%), and a trend toward prolonged PFS (8.4 vs. 3.6\u00a0months) as compared to patients with the complementary genotype. FC\u03b3R polymorphisms did not influence OR\/PFS\/TS.<\/jats:p><jats:p>These data show that clinical response to BEMPEG plus nivolumab treatment in the PIVOT-02 trial may be associated with the repertoire of KIR\/KIR-ligands an individual inherits. Further investigation and validation of these results may enable KIR\/KIR-ligand genotyping to be utilized prospectively for identifying patients likely to benefit from certain cancer immunotherapy regimens.<\/jats:p>","DOI":"10.1007\/s00262-023-03383-w","type":"journal-article","created":{"date-parts":[[2023,2,23]],"date-time":"2023-02-23T18:02:21Z","timestamp":1677175341000},"page":"2099-2111","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Associations between KIR\/KIR-ligand genotypes and clinical outcome for patients with advanced solid tumors receiving BEMPEG plus nivolumab combination therapy in the PIVOT-02 trial"],"prefix":"10.1007","volume":"72","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9349-4534","authenticated-orcid":false,"given":"A. 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