We assessed TIL expression of interleukin-2 (IL-2), IL-4, tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), granulocyte-macrophage colony stimulating factor (GM-CSF), IL-10, and transforming growth factor-beta (TGF-beta), and tumor cell expression of IL-10 and TGF-beta in situ in 49 primary colon carcinomas and 20 metastases using immunohistochemistry.
Analysis of the metastatic lesions showed that they expressed TGF-beta1 and MMP-2 but barely detectable levels of IL-10 or TIMP-1, suggesting that IL-10 and TIMP-1 might normally block tumor growth, angiogenesis, and metastasis.
Patients with lymphnode metastases and poorly differentiated tumours expressed IL-4 and IL-10 more frequently with concomitant suppression of IFN-gamma and IL-2 genes.
Moreover, stromal and immunological cells and their cytokines coordinate critical pathways that exert important roles in the ability of tumors to invade and metastasize, thus suppressive cytokines (IL-6 and IL-10) and neutralizing specific antibodies might subvert conditions for metastasis.
To investigate the local immunosuppressive microenvironment, we examined the presence of suppressor T lymphocytes and tolerising dendritic cells (DCs), the expression of immunosuppressive cytokines (IL-10, TGFbeta1 and TGFbeta2) and the enzyme indoleamine 2,3-dioxygenase (IDO) using qRT-PCR and immunohistochemistry in primary skin melanomas, negative and positive sentinel lymph nodes (SLN), and lymph nodes with advanced metastases.
Alterations of immunity by IL-10 derived from melanoma cells and melanoma-associated macrophages and lymphocytes potentially facilitate evolution of the primary melanoma and render regional lymph nodes susceptible to metastases.
Taken together, our findings establish that endogenous IL-10 inhibits inflammatory cytokine production and hampers the development of Treg cells and MDSCs, two key components of the immunosuppressive tumor microenvironment, thereby inhibiting tumor development, growth, and metastasis.
Regulatory T-cell depletion and IL-10 neutralization led to increased occurrence of vitiligo that correlated with a decreased incidence of melanoma metastases.
Further analyses revealed that the IL-10-1082A/G (rs1800896) genotypes were associated with advanced tumor stages and metastasis in osteosarcoma patients.
These results suggest that CD163<sup>+</sup>CD204<sup>+</sup> TAMs possibly play a key role in the invasion and metastasis of OSCC by T-cell regulation via IL-10 and PD-L1 production.
In addition, there was an increase in the number of patients positive for IL-10 upregulation within metastatic tumors when compared with primary tumors.
In tumor tissue, expression of IL17A was correlated with NOS2 (r = 0.68; p = 0.005), while in distant metastasisIL10 was in strong relation with TGFB1 and IL6.
IL-35 suppresses autoimmune diseases while preventing host defense to infection and promoting tumor growth and metastasis by converting resting B and T cells into IL-10-producing and IL-35-producing regulatory B (Breg) and T (Treg) cells.
Significant difference was noticed in the survival of SCC-Ag negative group compared with that of SCC-Ag positive group (P < .05).Serum IL-6, IL-8, IL-10, SCC-Ag, and CYFRA 21-1 were considered as potential markers in the metastasis and prognosis of breast cancer.
Reduction of pLTA-mediated IL-10 inhibited the metastasis of breast cancer cells (MDA-MB-231), which was induced by IL-10 or conditioned media prepared from PGE-2+LPS-stimulated PMA-differentiated THP-1 cells.
Serum levels of IL-8 and IL-10 of patients with malignant ovarian tumors in stable condition after chemotherapy were lower than those with recurrence and metastasis after chemotherapy (P<0.001).