Tumor Growth Alters T Cell and Macrophage Production of and Responsiveness to Granulocyte-Macrophage Colony-Stimulating Factor: Partial Dysregulation through Interleukin-10

Tumor-induced immune dysfunction: the macrophage connection

“…Although these molecules directly restrain T cell proliferation, only the inhibition of lipocortin, PGE 2 , ROI, and NO production blocks M-mediated suppression in the TBH. The increased M output of autoinhibitory TGF-␤ 1 and IL-10 during tumor growth controls the production of other M suppressor molecules; PGE 2 , NO, TNF-␣ [8,40], and enhancing molecules such as GM-CSF [6] are triggered through autocrine induction. For example, normal host Ms slightly curb T cell proliferation to maintain homeostasis, and antibody-mediated neutralization of TGF-␤ 1 and IL-10 relieves normal host M-mediated suppression of T cell proliferation [8,40].…”

“…Both fibrosarcoma cells and suppressive Ms produce significant amounts of IL-10 and TGF-␤ 1 [6,7], which may directly or indirectly block IL-12 synthesis. For example, NO induces M IL-12 gene expression [183].…”

“…An up-regulatory molecule produced and used by Ms and T cells during immunogenic challenge [186], GM-CSF activities during cancer are not well defined. GM-CSF normally enhances M activation [17] and accessory function [187] and increases MHC class II molecule expression [188]; however, these activities are inhibited by tumor growth [6,81,82,189]. In the TBH, Ms produce lower levels of, and are hyporesponsive to, GM-CSF [6].…”

“…Our studies [1][2][3][4][5][6][7][8] show a direct causal relationship between tumor presence and immune dysfunction, suggesting that the proximity of neoplastic tissue leads to immunologic degeneration. Although the importance of macrophages (Ms) in tumor-induced immune dysfunction is controversial, recent research suggests that the cellular basis for suppression includes the generation of immunoregulatory Ms that inhibit T cell responses and that are tumoricidally dysfunctional.…”

Effect of Arrabidaea chica extracts on the Ehrlich solid tumor development

“…Tumor growth initiates a myriad of functional and phenotypic changes in macrophages and T-cells in association with alterations in cytokine synthesis and responsiveness (Walker et al 1994). Several types of tumor also express receptors for granulocyte-macrophage colony stimulating factors or produces and uses granulocytemacrophage colony stimulating factors as an autocrine growth factor (Fu et al, 1991).…”