Influence of number of activating KIRs on Disease Free Survival: none vs. one vs. two activating KIRs.

<p>Patients who have two activating KIRs in their genotype have longer DFS compared to those who have one activating KIR. Patients who lack any activating KIR have the shortest DFS: no KIR: 54 months (CI: 42–65); one KIR: 77 months (CI: 61–92); two KIRs: 98 months (CI: 87–108) (p = 0.004). X axis shows percentage of survivors without recurrence against months of follow-up (y axis).</p

Comparison of KIR and KIR ligand genotype frequencies between patients recurring vs. those who did not.

<p>*: Combination of Group C and any cognate inhibitory KIR</p><p>Comparison of KIR and KIR ligand genotype frequencies between patients recurring vs. those who did not.</p

Characteristics of patients.

<p>n.s.: non significant</p><p>Characteristics of patients.</p

Comparison of KIR/Ligand frequencies: local recurrence versus distant metastasis.

<p>The variables found significant after comparison of frequencies between recurrent vs. non-recurrent cases were used in this table.</p

Impact of inhibitory (2DL1, 2DL1-Group C2 and 2DL3 Group C1) (upper row) and activating (2DS2, 2DS2- Group C1 and 2DS3) (lower row) KIRs on Progression Free Survival.

<p>X axis shows percentage of survivors without recurrence against months of follow-up (y axis). The lack of inhibitory KIR2DL1, 2DL1-C2, or 2DL3-C1 improved DFS (100% vs. 62.3%, p = 0.05; 93.8% vs. 60.0%, p = 0.035; 73.6% vs. 55.9%, p = 0.07). Presence of activating KIR2DS2, 2DS2-C1 and 2DS3 (77.8% vs. 48.5%, p = 0.01; 76.9% vs. 51.4%, p = 0.023; 79.4% vs. 58.5%, p = 0.003;) are also associated with longer DFS.</p

Impact Of “Killer Immunoglobulin-Like Receptor /Ligand” Genotypes On Outcome Following Surgery Among Patients With Colorectal Cancer: Activating Kirs Are Associated With Long-Term Disease Free Survival

Approximately 30 % of patients with stage II/III colorectal cancer develop recurrence following surgery. How individual regulation of host mediated anti-tumor cytotoxicity is modified by the killer-cell immunoglobulin-like receptor (KIRs) genotype is essential for prediction of outcome. We analyzed the frequency of KIR and KIR ligand Human Leukocyte Antigen Class I genotypes, and their effects on recurrence and disease-free survival (DFS). Out of randomly selected 87 colorectal cancer patients who underwent R0 resection operations between 2005 and 2008, 29 patients whose cancers progressed within a median five-year follow-up period were compared with 58 patients with no recurrence within the same time period. Recurrent cases shared similar tumor stages with non-recurrent cases, but had different localizations. We used DNA isolated from pathological archival lymphoid and tumor tissues for KIR and KIR ligand (HLA-C, group C1, group C2, and HLA-A-Bw4) genotyping. Among cases with recurrence, KIR2DL1 (inhibitory KIR) and A-Bw4 (ligand for inhibitory KIR3DL1) were observed more frequently (p=0.017 and p=0.024); and KIR2DS2 and KIR2DS3 (both activating KIRs) were observed less frequently (p=0.005 and p=0.043). Similarly, in the non-recurrent group, inhibitory KIR-ligand combinations 2DL1-C2 and 2DL3-C1 were less frequent, while the activating combination 2DS2-C1 was more frequent. The lack of KIR2DL1, 2DL1-C2, and 2DL3-C1 improved disease-free survival (DFS) (100% vs. 62.3%, p=0.05; 93.8% vs. 60.0%, p=0.035; 73.6% vs. 55.9%, p=0.07). The presence of KIR2DS2, 2DS3, and 2DS2-C1 improved DFS (77.8% vs. 48.5%, p=0.01; 79.4% vs. 58.5%, p=0.003; 76.9% vs. 51.4%, p=0.023). KIR2DS3 reduced the risk of recurrence (HR=0.263, 95% CI = 0.080-0.863, p=0.028). The number of activating KIRs are correlated strongly with DFS, none/ one/ two KIR : 54/77/98 months (p=0.004). In conclusion the inheritance of increasing numbers of activating KIRs and lack of inhibitory KIRs, independent of tumor localization or stage, is associated with long-term DFS.PubMedWoSScopu