Current status of interleukin-10 and regulatory T-cells in cancer

Abstract

Purpose of review Tumor growth elicits antigen-specific cytotoxic as well as immune suppressive responses. Interleukin-10 (IL-10) is a key immune-suppressive cytokine produced by regulatory T-cells (Tregs) and by helper T-cells (TH). Here we review pleiotropic functions of IL-10 that impact the immune pathology of cancer. Recent findings The role of IL-10 in cancer has become less certain with knowledge of its immune stimulatory functions. IL-10 is needed for T-helper cell functions, T-cell immune surveillance, and suppression of cancer-associated inflammation. By promoting tumor specific immune surveillance and hindering pathogenic inflammation IL-10 is emerging as a key cytokine in the battle of the host against cancer. Summary IL-10 functions at the cross roads of immune stimulation and immune suppression in cancer. Immunological mechanisms of action of IL-10 can be ultimately exploited to develop novel and effective cancer therapies.

Cholera-Toxin Suppresses Carcinogenesis in a Mouse Model of Inflammation-Driven Sporadic Colon Cancer

“…Using an exogenous IL-10 administration strategy and various mouse models of CRC we have consistently shown over the last years that IL-10 is suppressing carcinogenesis (9,36,38). The results of the present study add value to the key role of IL-10 in protecting mucosal surfaces from cancer (40).…”

“…The role of Treg in cancer is paradoxical (6,40,41). Treg have been traditionally viewed as cancerpromoting cells based on their function to suppress protective antineoplastic immune responses (40,41). However, our original studies in mice showing that the adoptive transfer of Treg not only protected but it further counteracted already established intestinal, breast and prostate neoplasia (6,9,10,25,36,42,43), are now supported by many other animal and human studies (8,40,41).…”

“…Also, because CT is known to have a profound effect in expanding Treg through enhancing antigen presentation by activated professional antigen cells and B-lymphocytes (16,17,19). The role of Treg in cancer is paradoxical (6,40,41). Treg have been traditionally viewed as cancerpromoting cells based on their function to suppress protective antineoplastic immune responses (40,41).…”

Folic acid-functionalized polyethylenimine superparamagnetic iron oxide nanoparticles as theranostic agents for magnetic resonance imaging and PD-L1 siRNA delivery for gastric cancer

“…27 IL10 is an immunosuppressive cytokine secreted by T cells and has been shown to be stimulated by PD-L1. 41,42 This change in cytokine secretions indicated effective PD-L1 knockdown and enhanced cytotoxic T-cell function. It has been demonstrated that CD8 + T cell inflaming GCs contain high PD-L1 expression, suggesting that adaptive immune resistance is active in GC.…”

Modulating gut immunity and neoplasia with oral cytokine adjuvants

“…3 In the context of inflammation-driven intestinal dysplasia, IL-10-production by T-regulatory cells is essential in the control of tumorigenesis. 4 Similarly, recombinant IL-10 can ameliorate disease symptoms in murine models of inflammatory bowel disease (IBD). 5 However, the results of clinical trials in IBD patients have been disappointing due to dose-limiting systemic toxicity.…”