Analyses on the Clinical Usefulness of Natural Killer Cell Activity in Non-Small Cell Lung Cancer Patients

Abstract

SESSION TITLE: Lung Cancer Diagnostics SESSION TYPE: Original Investigation Slide PRESENTED ON: Wednesday, November 1, 2017 at 02:45 PM - 04:15 PM PURPOSE: Natural killer (NK) cells have a potent cytolytic activity against malignant tumor cells. But in immune escape, the immunosuppressive tumor microenvironment impairs NK cell activity and then causes cancer progression. This study is aimed at investigating the alteration of NK cell activity in non small cell lung cancer (NSCLC) and the role of NK cell activity in advanced NSCLC after immune escape. METHODS: A prospective observational study evaluating NK cell activity and other clinical factors was conducted in a tertiary hospital between January 2016 and February 2017. NK cell activity was measured by NK vue® kit which detected ex vivo stimulated IFN-r levels of the peripheral blood by ELISA. NK cell subsets were measured by flow cytometry. The correlation of NK cell activity with other clinical factor including Age, smoking history, smoking quantity, NK cell subsets proportion (CD56bright/CD56dimcells ratio, Geometric mean of CD56brightcells), tumor marker (CEA, CYFRA 21-1) and CRP were analyzed by linear regression. All results are presented as mean ± SD. RESULTS: 48 patients of NSCLC (stage I: 13, stage II: 7, stage III: 8, stage IV: 20), 38 patients of benign lung disease and 33 healthy controls were recruited. There were 33 adenocarcinoma, 13 squamous cell carcinoma, 1 large cell carcinoma and 1 NOS patents. NK cell activity was significantly reduced in NSCLC patients compared to controls and benign lung disease patients (1660±878.7 vs 1516±1066 vs 958.7±1011 pg/mL for control vs benign lung disease vs NSCLC, respectively; p<0.05). NK cell activity tended to decrease according to cancer stage progression (1924±953.4 vs 890.0±971.8 vs 356.7±523.0 vs 596.1±791.4 for stage I vs stage II vs stage III vs stage IV, respectively) and significantly decreased in advanced stage compared to early stage (1562±1062 vs 527.7±723.7 pg/mL for stage I, II vs stage III, IV, respectively; p=0.0001). NK cell activity was significantly reduced in nodal positive NSCLC compared to nodal negative NSCLC (1494±1083 vs 637.2±827.9 pg/mL for NO vs N1, N2, N3, respectively; p=0.0025). CD56brightcells/CD56dimcells ratio (0.0326±0.0406 vs 0.0318±0.0180 vs 0.0311±0.0233 for control vs benign lung disease vs NSCLC, respectively; p=0.4496) and geometric mean of CD56brightcells (185.4±62.45 vs 203.8±75.49 vs 166.8±45.77 for control vs benign lung disease vs NSCLC, respectively; p=0.1507) were not different between the three groups. Other clinical factors including Age, smoking history, smoking quantity, NK cell subsets, tumor marker and CRP were not correlated with NK cell activity by univariate and multivariate analyses. CONCLUSIONS: NK cell activity decreased significantly in NSCLC patients and was further reduced in advanced stage and nodal positive NSCLC. CD56brightcells/CD56dimcells ratio and other clinical factors did not affect NK cell activity. CLINICAL IMPLICATIONS: Decreased NK cell activity may reflect immune escape in NSCLC progression and NK cell activity may have a role of biomarker of advanced lung cancer. DISCLOSURE: The following authors have nothing to disclose: Sue In Choi, Kwnag Ho In, Kyung Ho Kang, Jae Jeong Shim, Chol Shin, Sang Yeub Lee, Je Hyeong Kim, Sung Yong Lee, Seung Heon Lee, Gyu Young Hur, Kyung Hoon Min, Eun Joo Lee, Won Jai Jung No Product/Research Disclosure Information