Differential expression of chemokines, chemokine receptors, cytokines and cytokine receptors in diffuse large B cell malignant lymphoma.
Host immunity, particularly T cell immunity (Th1/Th2 balance), plays an important role in clinicopathological features of malignant disease. However, the T cell immunity has not been fully investigated in patients with lymphoid malignancies. Recent studies suggested the important role of dysregulation of the endogenous immune system in lymphomagenesis. The relationships between cytokines/chemokines and their receptors, are important in determining the selectivity of local immunity. To investigate differences in the endogenous immune system of diffuse large B cell lymphoma (DLBL), we performed gene expression profiling using cDNA microarrays of cytokines/chemokines and their receptors. We studied 5 cases each of primary central nervous system lymphomas (PCNSL), extranodal and nodal lymphomas. PCNSL exhibited diffuse down-regulated profiles, compared to normal peripheral blood lymphocytes. While extranodal and nodal lymphomas also exhibited diffuse down-regulated profiles, some genes displayed up-regulated profiles. Hierarchical clustering analysis separated PCNSL and extranodal lymphomas into distinct groups based on their gene expression profiles, as well as extranodal and nodal, but not PCNSL and nodal. PCNSL exhibited significantly lower expression of BLC/BCA-1 and CCR-3 (Th2 type), and higher expression of IL-8 and MIP-1beta (Th1 type) than extranodal lymphomas. Immunohistochemistry and RT-PCR revealed frequent CCR-3 and BLC/BCA-1 expression in extranodal lymphomas, compared with PCNSL. Our results provide new insights into the pathogenesis of each DLBL. A better understanding of the immune response in each DLBL could help in the design of novel therapeutic strategies based on cytokines/chemokines and their receptors.
Fujii
Akira
A
Department of Pathology, Fukuoka University School of Medicine, Jonan-ku, Fukuoka 814-0180, Japan. afujii@minf.med.fukuoka-u.ac.jp
Ohshima
Koichi
K
Hamasaki
Makoto
M
Makimoto
Yoshifumi
Y
Haraoka
Seiji
S
Utsunomiya
Hidetsuna
H
Okazaki
Masatoshi
M
Kikuchi
Masahiro
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D054382:Chemokine CXCL13; D018925:Chemokines / Q000096:biosynthesis*; D019743:Chemokines, CXC / Q000096:biosynthesis; D016207:Cytokines / Q000096:biosynthesis*; D018076:DNA, Complementary / Q000378:metabolism; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008214:Lymphocytes / Q000378:metabolism; D016403:Lymphoma, Large B-Cell, Diffuse / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D005810:Multigene Family; D020411:Oligonucleotide Array Sequence Analysis; D054397:Receptors, CCR3; D019707:Receptors, Chemokine / Q000096:biosynthesis*; D018121:Receptors, Cytokine / Q000096:biosynthesis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000378:metabolism; D015854:Up-Regulation
C515350:CCR3 protein, human; C110663:CXCL13 protein, human; D054382:Chemokine CXCL13; D018925:Chemokines; D019743:Chemokines, CXC; D016207:Cytokines; D018076:DNA, Complementary; D054397:Receptors, CCR3; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine