Abstract
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.
Highlights
Angioimmunoblastic T-cell lymphoma (AITL) is the second most common subtype of peripheral T-cell lymphomas (PTCLs) according to the InternationalT-Cell Lymphoma Project [1]
Other interleukins failed to show a significant association with survival, elevated serum level of IL-10 was significantly associated with a poor response to CHOP chemotherapy as well as inferior overall survival (Figure 2C)
Subgroup analysis showed that this association of serum IL-10 with survival was only significant in AITL patients (Figure 3A)
Summary
Angioimmunoblastic T-cell lymphoma (AITL) is the second most common subtype of peripheral T-cell lymphomas (PTCLs) according to the InternationalT-Cell Lymphoma Project [1]. GATA3 is a transcription factor related to type 2-helper (Th2) cells; high GATA3 expression can induce Th2-associated cytokines such as interleukin (IL)-4, IL-5, IL-10, and IL-13 [6] As interleukins such as IL-4 and IL10 can increase the level of M2 polarized macrophages, inhibiting the anti-tumor effect of non-neoplastic T-cells, Th2-associated cytokines can influence the tumor microenvironment to promote tumor progression [7]. Consistent with the effects of GATA3 and Th2-associated cytokines on the tumor microenvironment, a recent study demonstrated the correlation of GATA3 expression with macrophage infiltration of the tumor, resulting in poor prognosis in patients with PTCL [8]. There are few studies on the role of serum GATA3-related cytokines in the promotion of type 2-helper cells, the so-called Th2associated cytokines, and tumor-associated macrophages in patients with AITL. We analyzed the prognostic value of M2 polarized macrophages in AITL to demonstrate the role of Th2-associated cytokines and tumor-associated macrophages in the aggressiveness of AITL
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