KIR 2D (L1, L3, L4, S4) and KIR 3DL1 protein expression in non-small cell lung cancer

Oncotarget. 2016 Dec 13;7(50):82104-82111. doi: 10.18632/oncotarget.13486.

Abstract

Background: Nature killer (NK) cells are the immune system's first line of defense against both viral infections and tumors. Killer cell immunoglobulin-like receptors (KIRs) are associated with susceptibility to different types of cancers. We investigated KIR 2D (L1, L3, L4, S4) and KIR 3DL1 protein expression and their association with survival in non-small cell lung cancer (NSCLC).

Methods: The expression of KIR 2D (L1, L3, L4, S4) (BC032422/ ADQ31987/ NP_002246/ NP_036446, ABCAM) and KIR 3DL1 (AA 1-444, ABCAM) protein was assessed by immunohistochemistry (IHC) in 62 NSCLC patients.

Results: KIR 2D (L1, L3, L4, S4) and KIR 3DL1 were expressed both on NSCLC tumor cells and tumor infiltrating lymphocytes (TILs). Fourteen samples (22.6%) stained positive for KIR 2D (L1, L3, L4, S4) on the tumor cells, and 10 (16.1%) had positive expression on the TILs. Thirty-three samples (53.2%) stained positive for KIR 3DL1 on the tumor cells, and 31 (50.0%) had positive expression on the TILs. Patients with negative KIR 2D (L1, L3, L4, S4) expression on tumor cells or TILs had longer overall survival (OS) than patients who are KIR 2D (L1, L3, L4, S4) positive on tumor cells (40.70 weeks, 95% CI 24.76-56.65 vs. 7.10 weeks, 95% CI 0.00-19.38, P = 0.014) or TILs (40.70 weeks, 95% CI 24.05-57.35 vs. 3.90 weeks, 95% CI 0.00-9.17, P < 0.001). Likewise, longer OS was significantly correlated with negative expression of KIR 3DL1 on tumor cells (62.30 weeks, 95% CI 0.00-177.37 vs. 13.10 weeks, 95% CI 3.42-22.78, P < 0.001) or TILs (62.30 weeks, 95% CI 0.00-152.05 vs. 12.10 weeks, 95% CI 2.61-21.59, P < 0.001). Cox regression analysis showed that KIR 2D (L1, L3, L4, S4) on TILs was correlated with OS (P = 0.032, Odds Ratio 2.628 95%CI 1.089-6.340).

Conclusions: KIR 2D (L1, L3, L4, S4) and KIR 3DL1 expression was correlated with poor prognosis in NSCLC patients.

Keywords: KIR 2D (L1, L3, L4, S4); KIR 3DL1; NSCLC; Pathology Section.

MeSH terms

  • Aged
  • Biomarkers, Tumor / analysis*
  • Carcinoma, Non-Small-Cell Lung / chemistry*
  • Carcinoma, Non-Small-Cell Lung / mortality
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Female
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Logistic Models
  • Lung Neoplasms / chemistry*
  • Lung Neoplasms / immunology
  • Lung Neoplasms / mortality
  • Lung Neoplasms / pathology
  • Lymphocytes, Tumor-Infiltrating / chemistry*
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Lymphocytes, Tumor-Infiltrating / pathology
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Odds Ratio
  • Prognosis
  • Proportional Hazards Models
  • Receptors, KIR / analysis*
  • Receptors, KIR2DL1 / analysis*
  • Receptors, KIR2DL3 / analysis*
  • Receptors, KIR2DL4 / analysis*
  • Receptors, KIR3DL1 / analysis*
  • Retrospective Studies
  • Risk Factors
  • Time Factors

Substances

  • Biomarkers, Tumor
  • KIR2DL1 protein, human
  • KIR2DL3 protein, human
  • KIR2DL4 protein, human
  • KIR2DS4 protein, human
  • KIR3DL1 protein, human
  • Receptors, KIR
  • Receptors, KIR2DL1
  • Receptors, KIR2DL3
  • Receptors, KIR2DL4
  • Receptors, KIR3DL1