Elevated serum interleukin-10 level and M2 macrophage infiltration are associated with poor survival in angioimmunoblastic T-cell lymphoma

Interleukin-10 (IL-10) induces an immunosuppressive microenvironment including M2 macrophages, inhibiting anti-tumor immunity. The aim of this study was to evaluate whether serum IL-10 level at diagnosis and tissue infiltration of M2 macrophages could predict survival outcome of patients with angioimmunoblastic T-cell lymphoma (AITL). We measured serum levels of IL-5, IL-10, IL-12, and interferon-gamma (IFN-γ) at diagnosis in AITL and other common subtypes of nodal T-cell lymphoma including peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS), ALK-negative anaplastic large cell lymphoma (ALCL) or ALK-positive ALCL between September 2008 and December 2014. We also analyzed the infiltration of CD68- and CD163-positive macrophages in tumor tissue of AITL. In total, 97 patients with AITL (n=37), PTCL-NOS (n=40), ALK-negative ALCL (n=11), or ALK-positive ALCL (n=9) were treated with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone). Among cytokines, only the serum level of IL-10 was significantly higher in AITL patients than in other subtypes (P < 0.05). Compared to other subtypes, the association of serum IL-10 with overall survival (OS) was only significant in AITL. Accordingly, the response to CHOP chemotherapy was significantly worse in the high IL-10 group, and infiltration of CD163-positive M2 macrophages was significantly associated with OS in AITL. In conclusion, this study demonstrated the prognostic relevance of serum IL-10 and tissue infiltration of M2 macrophages in AITL patients. Our results suggest the possible use of these variables as potential therapeutic targets and novel prognostic indicators in patients with AITL.