Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:Q06643 (non-Hodgkin's lymphoma)
 11,307 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tumor-infiltrating CD8+ T-lymphocytes (T-TILs) are thought to be relevant to immunosurveillance of several tumor types including B-cell non-Hodgkin's lymphoma. B- and T-lymphocyte interactions via cellular adhesion molecules (CAMs), recognition molecules (HLAs), and costimulatory molecules (CSMs) are necessary for optimal antigen-specific T-cell activation to occur and may be important in generating effective host T-TIL responses. We previously found that low T-TIL response (CD8+ T cells < 6%) correlates with statistically shorter relapse-free survival in patients with diffuse large-cell lymphoma (DLCL). We now extend our observations in 71 DLCL patients by analyzing malignant B-cell expression of the following molecules important in T-cell activation: (a) recognition molecules [MHC I (MAS and MCA) and MHC II (HLA-DR, -DP, -DQ)]; (b) CAMs [leukocyte function antigen 1 (CD11a and CD18) and intracellular adhesion molecule 1 (CD54)]; and (c) CSMs [B7.1 (CD80) and B7.2 (CD86)]. Eighteen patients (25%) had low a T-TIL response, and 53 patients (75%) had a high T-TIL response. Overall, expression of the MHC class H molecules HLA-DR and HLA-DQ was most conserved. The loss of B7.2 (P = 0.04), intracellular adhesion molecule 1 (P = 0.0004), MAS (P = 0.02), and HLA-DR (P = 0.0004) expression was significantly associated with decreased T-TIL response. In 100% of patients with low T-TIL responses, at least one HLA, CAM, or CSM was undetectable on the malignant B cells by immunohistochemical staining (mean number of molecules lost = 2.67). In contrast, 49% of patients with high T-TIL responses had no losses in HLA, CAM, or CSM expression (mean number of molecules lost = 0.89). The mean number of absent molecules (HLA, CAM, or CSM) was significantly associated with T-TIL response (P = 0.0001). We conclude that loss of HLA, CAM, or CSM expression on malignant B cells is associated with a poor host T-cell immune response. In addition, because patients with low T-TIL response had lost expression of multiple cellular adhesion, recognition, and costimulatory molecules, our results suggest that a combination of immunorestorative therapies may be required to generate effective antitumor T-cell responses in B-cell DLCL.
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PMID:Loss of B7.2 (CD86) and intracellular adhesion molecule 1 (CD54) expression is associated with decreased tumor-infiltrating T lymphocytes in diffuse B-cell large-cell lymphoma. 1105 Dec 36

Several studies have shown the existence of an association between celiac disease (CD) and non-Hodgkin's lymphoma (NHL). Our aim was to evaluate the usefulness of the serum anti-tissue transglutaminase (anti-tTG) antibody assay in screening for CD in consecutive NHL patients. In all, 80 consecutive patients (median age 61 years) with a new diagnosis of NHL were included. To compare the frequency of CD and of positive results for the anti-tTG assay, we enrolled 500 blood donors. In all patients serum anti-tTG was determined with two different ELISA: one based on tTG from guinea pig (gp-tTG) and the other based on human recombinant t-TG (h-tTG) as the antigens. Serum anti-endomysial antibodies (EmA) were also assayed. Subjects with positive serum EmA and/or anti-tTG underwent intestinal biopsy for histology study, HLA-DQ phenotype determination, and serum anti-gliadin (AGA) assay. Eight of 80 (10%) NHL patients were positive for anti-tTG ELISA--two of these exclusively for anti-gp-tTG and six for anti-h-tTG (7.5%). None of the 80 NHL patients were positive for serum EmA. The frequency of anti-tTG positivity in the blood donor controls was 2/500 (0.4%), significantly lower than that observed in the NHL patients (P < 0.0001). Both these blood donors were found to have CD. Only in one anti-h-tTG-positive NHL patient was there intestinal mucosa atrophy, and follow-up confirmed a CD diagnosis (CD frequency in NHL patients is 1.2%; versus blood donors: P = 0.4). In all the other seven anti-tTG-positive NHL patients a normal intestinal architecture was found, although, inflammatory infiltration of the lamina propria was observed in four patients. No anti-tTG-positive NHL patients, including the subject diagnosed as having CD, had a family history of CD, and all had normal weight and no signs of malabsorption. Anti-tTG false positive results were associated with a higher frequency of serum autoantibody positivity and T-cell type NHL. In conclusion, NHL patients the anti-tTG assay often gives discordant data with the EmA assay, with a high frequency of anti-tTG false positive results for CD diagnosis.
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PMID:Screening for celiac disease in non-Hodgkin's lymphoma patients: a serum anti-transglutaminase-based approach. 1292 48