Activated leukocyte cell adhesion molecule as a biomarker for disease severity and efficacy of sublingual immunotherapy in allergic rhinitis.

BACKGROUND: Activated leukocyte cell adhesion molecule (ALCAM) plays an important role in T cell activation and immune response, but the role of ALCAM in allergic rhinitis (AR) remains unclear. The objective of the current study was to validate serum ALCAM as a biomarker in assessing disease severity and predicting the efficacy of sublingual immunotherapy (SLIT) in AR patients. METHODS: We recruited 40 healthy controls (HC group), 38 mild AR patients (MAR group) and 80 moderate-severe AR patients (MSAR group) in this study. Serum levels of ALCAM were determined by ELISA, and the association between ALCAM levels and disease severity was evaluated. In the MSAR group, 68 patients underwent and finished 3-years of SLIT, and were divided into effective group and ineffective group, the relationship between ALCAM levels and efficacy of SLIT was exampled. RESULTS: ALCAM levels were elevated in the serum of AR patients in comparison with HC. Moreover, serum ALCAM concentrations were higher in MSAR group than in MAR group and HC group, and levels of ALCAM significantly correlated with AR total nasal symptom score (TNSS) (r = 0.330, P < 0.001), visual analogue scale (VAS) (r = 0.387, P < 0.001) and serum total IgE levels (r = 0.442, P < 0.001). In the effective group, the ALCAM levels were significantly lower than in the ineffective group. Receiver operating characteristic (ROC) curve exhibited good accuracy for predicting clinical efficacy of SLIT (area under the curve = 0.805, P < 0.001). CONCLUSIONS: The serum ALCAM maybe a novel biomarker for assessing disease severity and predicting clinical efficacy of SLIT in AR patients.

Activated leucocyte cell adhesion molecule (ALCAM/CD166) regulates T cell responses in a murine model of food allergy.

Food allergy is a major public health problem. Studies have shown that long-term interactions between activated leucocyte cell adhesion molecule (ALCAM/CD166) on the surface of antigen-presenting cells, and CD6, a co-stimulatory molecule, influence immune responses. However, there are currently no studies on the functions of ALCAM in food allergy. Therefore, we aimed to identify the functions of ALCAM in ovalbumin (OVA)-induced food allergy using ALCAM-deficient mice. Wild-type (WT) and ALCAM-deficient (ALCAM-/- ) mice were sensitized intraperitoneally and with orally fed OVA. The mice were killed, and parameters related to food allergy and T helper type 2 (Th2) immune responses were analysed. ALCAM serum levels increased and mRNA expression decreased in OVA-challenged WT mice. Serum immunoglobulin (Ig)E levels, Th2 cytokine mRNA and histological injuries were higher in OVA-challenged WT mice than in control mice, and these were attenuated in ALCAM-/- mice. T cell proliferation of total cells, CD3+ CD4+ T cells and activated T cells in immune tissues were diminished in OVA-challenged ALCAM-/- mice. Proliferation of co-cultured T cells and dendritic cells (DCs) was decreased by the anti-CD6 antibody. In addition, WT mice sensitized by adoptive transfer of OVA-pulsed ALCAM-/- BM-derived DCs showed reduced immune responses. Lastly, serum ALCAM levels were higher in children with food allergy than in control subjects. In this study, serum levels of ALCAM were elevated in food allergy-induced WT mice and children with food allergy. Moreover, immune responses and T cell activation were attenuated in OVA-challenged ALCAM-/- mice. These results indicate that ALCAM regulates food allergy by affecting T cell activation.

Serum activated leukocyte cell adhesion molecule and intercellular adhesion molecule-1 in patients with gastric cancer: Can they be used as biomarkers?

Cellular adhesion molecules might be used as markers in diagnosis and prognosis in some types of malignant tumors. The purpose of this study was to determine the clinical significance of the serum levels of activated leukocyte cell adhesion molecule-1 (ALCAM) and intercellular adhesion molecule-1 (ICAM-1) in gastric cancer (GC) patients. Fifty-eight GC patients and 20 age- and sex-matched healthy controls were enrolled into this study. Pretreatment serum markers were determined by the solid-phase sandwich enzyme-linked immunosorbent assay (ELISA). The median age at diagnosis was 59.5 years (range 32-82 years). Tumor localizations of the majority of the patients were antrum (n=42, 72.4%) and tumor histopathologies of the majority of the patients were diffuse (n=43, 74.1%). The majority of the patients had stage IV disease (n=41, 70.7%). Thirty six (62.1%) patients had lymph node involvement. The median follow-up time was 66 months (range 1-97.2 months). At the end of the observation period, 26 patients (44.8%) were dead. The median survival for all patients was 21.4±5 months (%95 CI, 11.5-31.3). The 1-year survival rates were 66.2%. The baseline serum ALCAM levels of the patients were significantly higher than those of the controls (p=0.001). There was no significant difference in the serum levels of ICAM-1 between the patients and controls (p=0.232). No significant correlation was detected between the levels of the serum markers and other clinical parameters (p>0.05). Tumor localization (p=0.03), histopathology (p=0.05), and response to chemotherapy (p=0.003) had prognostic factors on survival. Neither serum ALCAM levels nor serum ICAM-1 levels were identified to have a prognostic role on overall survival (ICAM-1 p=0.6, ALCAM p=0.25). In conclusion, serum levels of ALCAM were found to have diagnostic value in GC patients.

ALCAM (CD166) expression and serum levels are markers for poor survival of esophageal cancer patients.

The expression of the activated leukocyte cell adhesion molecule (ALCAM and CD166) is increased in various types of cancer. We aimed to evaluate its role as a prognostic marker for esophageal cancer (EC). We retrospectively analyzed ALCAM expression in 299 primary lesions, 147 lymph node and 46 distant metastases from EC patients, on a tissue microarray using immunohistochemistry. Bone marrow samples from representative cancer patients (n = 16), taken before primary surgery, were stained by double-immunofluorescence for ALCAM and cytokeratins (CK). Blood serum samples from 236 cancer patients and 127 controls were analyzed for serum ALCAM (s-ALCAM) by ELISA. The immunohistochemical analysis showed increased ALCAM expression in the majority of lesions (primary tumor 71%, lymph node 76% and distant metastases 80%). ALCAM expression was not associated with histopathological parameters except for tumor grading (p = 0.015). ALCAM-positive patients had significantly worse recurrence-free and overall survival (OS; p = 0.002). Disseminated tumor cells (DTC) in bone marrow showed two phenotypes, ALCAM+/CK+ (36%) and ALCAM-/CK+ (64%). Multivariate analysis revealed that ALCAM expression and elevated s-ALCAM serum values are powerful prognostic variables for OS in patients with EC (hazard ratio [HR] 3.987, 95% confidence interval [95%CI] 1.906-8.340, p < 0.001 and HR 1.915, 95%CI 1.021-3.592, p = 0.043). The results of our study provide preliminary evidence for the potential clinical utility of ALCAM as a prognostic biomarker for EC, which might be a basis for future clinical application. In addition, ALCAM expression in a subset of DTC of the bone marrow indicates a potential function in the metastatic cascade of EC.

ALCAM is associated with chemoresistance and tumor cell adhesion in pancreatic cancer.

AIMS: Cell-cell adhesion is a major factor in integrity of epithelia which is frequently disturbed in cancer leading to local invasion and distant metastasis. METHODS: To define expression and function of activated leukocyte cell adhesion molecule (ALCAM, CD166) in pancreatic cancer and in pancreatic neuroendocrine tumors (PNET), microarray analyses, RT-PCR, immunohistochemistry, RNAi, adhesion, migration, invasion, and chemoresistance assays were used. RESULTS: We demonstrate that expression of ALCAM is altered and its serum levels are increased in pancreatic ductal adenocarcinoma (PDAC). ALCAM was expressed on the membranes of islet cells in the normal pancreas whereas normal pancreatic ducts were ALCAM-negative. In PDAC, ALCAM expression was generally rare though in some tumors, membranous, or cytoplasmic ALCAM was found. PNET were mostly ALCAM-positive with a cytoplasmic staining pattern which was in contrast to the membrane expression observed in non-transformed islet cells. In vitro, ALCAM silencing using RNAi had no effects on growth or invasion of pancreatic cancer cells but reduced cell adhesion and induced chemoresistance. In neuroendocrine tumor cell lines, silencing of ALCAM decreased cell growth. CONCLUSIONS: We propose ALCAM as a novel serum biomarker in human pancreatic tumors which is associated with cell adhesion, growth and chemoresistance.