Chronic lymphocytic leukemia cells induce changes in gene expression of CD4 and CD8 T cells.
To examine the impact of tumors on the immune system, we compared global gene expression profiles of peripheral blood T cells from previously untreated patients with B cell chronic lymphocytic leukemia (CLL) with those from age-matched healthy donors. Although the cells analyzed were not part of the malignant clone, analysis revealed differentially expressed genes, mainly involved in cell differentiation in CD4 cells and defects in cytoskeleton formation, vesicle trafficking, and cytotoxicity in CD8 cells of the CLL patients. In coculture experiments using CLL cells and T cells from healthy allogeneic donors, similar defects developed in both CD4 and CD8 cells. These changes were induced only with direct contact and were not cytokine mediated. Identification of the specific pathways perturbed in the T cells of cancer-bearing patients will allow us to assess steps to repair these defects, which will likely be required to enhance antitumor immunity.
Görgün
Güllü
G
Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Holderried
Tobias A W
TA
Zahrieh
David
D
Neuberg
Donna
D
Gribben
John G
JG
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D016022:Case-Control Studies; D018925:Chemokines / Q000235:genetics; D003598:Cytoskeletal Proteins / Q000235:genetics; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics* / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D020411:Oligonucleotide Array Sequence Analysis; D019707:Receptors, Chemokine / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics
D018925:Chemokines; D003598:Cytoskeletal Proteins; D004273:DNA, Neoplasm; D019707:Receptors, Chemokine