Dual biological effects of the cytokines interleukin-10 and interferon-γ

Abstract

It is generally thought that each cytokine exerts either immune stimulatory (inflammatory) or immune inhibitory (antiinflammatory or regulatory) biological activities. However, multiple cytokines can enact both inhibitory and stimulatory effects on the immune system. Two of these cytokines are interleukin (IL)-10 and interferon-gamma (IFNγ). IL-10 has demonstrated antitumor immunity even though it has been known for years as an immunoregulatory protein. Generally perceived as an immune stimulatory cytokine, IFNγ can also induce inhibitory molecule expression including B7-H1 (PD-L1), indoleamine 2,3-dioxygenase (IDO), and arginase on multiple cell populations (dendritic cells, tumor cells, and vascular endothelial cells). In this review, we will summarize current knowledge of the dual roles of both of these cytokines and stress the previously underappreciated stimulatory role of IL-10 and inhibitory role of IFNγ in the context of malignancy. Our progressive understanding of the dual effects of these cytokines is important for dissecting cytokine-associated pathology and provides new avenues for developing effective immune therapy against human diseases, including cancer.

Clinicopathologic analysis of programmed cell death-1 and programmed cell death-ligand 1 and 2 expressions in pulmonary adenocarcinoma: comparison with histology and driver oncogenic alteration status

“…6,34 During antitumor immune responses in vivo, various immune and tumor cells produce cytokines that upregulate PD-L1 (CD274) extrinsically in a paracrine and/or autocrine manner. 6,35 In contrast, an intrinsic mechanism refers to constitutive PD-L1 expression by oncogenic signaling, such as NPM-ALK translocation, PI3K/Akt activation, or chronic viral infection, 26,34,36 suggesting that intrinsic genetic alterations in tumor cells might account for regulation of the PD-1/PD-L pathway. Moreover, several driver mutations have emerged as therapeutic targets for patients with pulmonary adenocarcinoma.…”

Programmed death ligand 1 (PD-L1) expression influences the immune-tolerogenic microenvironment in antiretroviral therapy-refractory Kaposi's sarcoma: A pilot study

“…PD-L1 is upregulated by many cell types (epithelial, hematopoietic, and endothelial) in response to pro-inflammatory cytokines. 20 PD-L1 expression in either tumor cells or surrounding infiltrate has emerged as a predictive correlate of response to PD-1/PD-L1-targeted checkpoint inhibitors in a growing variety of solid tumors. 9 Hence, there is strong reason to seek to identify other tumors that may be using the same immune escape mechanism and therefore benefit from these remarkable novel therapies.…”

The role of the immune system in neurofibromatosis type 1-associated nervous system tumors

“…• IFN-γ IFN-γ plays a crucial role in inducing Th1 immune response through CD4 + T cells, leading to CTL recruitment in the tumor microenvironment [101]. CD8 + T cells express IFN-γ within tumor tissue that upregulates the immune checkpoint proteins PD-L1 on tumor cells and PD-1 on CD8 + T cells, shutting down a cytotoxic antitumor T-cell response [101][102][103].…”

“…CD8 + T cells express IFN-γ within tumor tissue that upregulates the immune checkpoint proteins PD-L1 on tumor cells and PD-1 on CD8 + T cells, shutting down a cytotoxic antitumor T-cell response [101][102][103]. IFN-γ may also affect the immune response in the brain by increasing the expression of proteins on BBB endothelial cells necessary for T-cell transmigration into the brain [33].…”