Imbalances of chemokines, chemokine receptors and cytokines in Hodgkin lymphoma: classical Hodgkin lymphoma vs. Hodgkin-like ATLL.

Abstract

Classical Hodgkin lymphoma (HL) is characterized by the presence of Hodgkin and Reed-Sternberg cells (H&RS) and a prominent lymphocytic infiltration. We previously reported Hodgkin-like adult T-cell leukemia/lymphoma (HL-like ATLL) (new WHO classification). Various CXC and CC chemokines are expressed on H&RS cells and the relationships between chemokines and the chemokine receptor (R) are thought to be important for selectivity of local immunity of Th1 and Th2 T cells. To clarify the role of T-cell immunity in classical HL and Hodgkin-like ATLL, we performed gene expression profiling (chemokine, chemokine R and cytokine DNA chips) in 12 cases [classical HL, 8 cases [mixed cellularity (MC) type, 4; nodular sclerosis (NS) type, 4]; Hodgkin-like ATLL, 4 cases] and immunohistochemical staining in 29 cases (MC, 10; NS, 10; Hodgkin-like ATLL, 9). EBV-infected H&RS cells were detected in 9 of 10 cases of HL MC, 5 of 9 of HL-like ATLL and 2 of 10 HL NS. T-cell-directed chemokine thymus- and activation-regulated chemokine (TARC)- and/or macrophage-derived chemokine (MDC)-positive H&RS cells were detected in all 20 cases of HL MC and HL NS but only in 5 of 9 cases of HL-like ATLL. Interferon-gamma-inducible protein-10 (IP10)- and monokine induced by interferon-gamma (MIG)-positive H&RS cells were detected in all 10 HL MC but only in 5 of 10 cases of HL NS and 2 of 9 cases of HL-like ATLL. However, 2 of 5 cases of HL-like ATLL with EBV infection and 2 of 2 HL NS with EBV had IP10/MIG-positive H&RS cells. The chemokine expressions in H&RS cells seemed to be associated with EBV infection rather than histologic subtypes. In the DNA chip expression analysis, classical HL and HL-like ATLL had a mixed Th1/Th2-type profile, and HL MC (EBV-positive) and HL NS (EBV-negative) were differentially clustered. However, 2 cases of HL-like ATLL clustered with HL MS and the other 2 cases of HL-like ATLL clustered with HL NS. The former HL-like ATLL had EBV infection in H&RS cells, whereas the latter did not have EBV infection. This finding also suggests that EBV might influence local expression of chemokines rather than HL subtypes. Our results indicate that local immunologic disorder or imbalance appears to influence the formation of H&RS cells and that in HL-like ATLL, HTLV-1 infection might not be necessary for H&RS cell formation.