Lentinan enhances the antitumor effects of Delta-like 1 via neutrophils

Abstract

Background Selective activation of Delta-like 1 (DLL1)-Notch signaling is a new approach to activate CD8+ T cell and suppress tumor growth, while the efficacy remains modest. Lentinan (LNT) is a clinically used immunomodulation agent. Thus, we hypothesized that LNT could improve the efficacy of DLL1. Methods The effects of LNT combined with DLL1 on tumor growth were evaluated by growth curve and tumor weight in EO771 breast and LAP0297 lung tumor models. The impacts on immune cells and gene expression in tumor tissues were determined by flow cytometry, qPCR. Neutrophil depletion was used to investigate the mechanism of the combination therapy on tumor growth. The data sets were compared using unpaired student’s t-test or ordinary one-way ANOVA. Results LNT treatments additively improved the antitumor effects of DLL1 in EO771 breast tumor growth. Remarkably, LNT treatments synergistically enhanced the suppression of DLL1 on LAP0297 lung tumor growth, resulting in tumor regression. Mechanically, the combination of LNT and DLL1 interventions not only promoted the accumulation and activation of CD8+ T cells, but also increased intratumoral CD45+CD11b+Ly6G+ neutrophils. Reduced neutrophils by anti-Gr1 antibody administrations reversed the improved antitumor effects by LNT treatments in LAP0297 lung tumor. These results suggest that LNT treatments improve the inhibition of DLL1 on tumor growth via neutrophils. Conclusions Our findings indicates that LNT and DLL1 may induce synergistical antitumor immunity via simultaneous modulating lymphoid and myeloid cell populations regardless of the type of tumor, providing a potential new strategy to potentiate cancer immunotherapy.

Smad3 is essential for polarization of tumor-associated neutrophils in non-small cell lung carcinoma

“…By contrast, neutrophil depletion in wild-type mice had no effect on tumor growth, arguing that despite a predominant N2 TAN protumor phenotype, they did not significantly impact tumor development. Indeed, the use of neutrophil depletion in mouse models of lung cancer have produced disparate results, with some showing antitumor effects 11 , 37 , some showing no effect 40 , 41 , and others showing enhanced growth and metastasis as a result of neutrophil depletion 42 , 43 . To further substantiate the function of N1 Smad3-KO neutrophils in lung cancer development, we performed adoptive transfer studies, which showed that delivery of Smad3-KO-BMDN, but not wild-type BMDN, could suppress tumor growth.…”

Traditional Chinese Medicine in Regulating Tumor Microenvironment

“…The effects on tumor cells are mainly reflected in the following aspects: (1) Inhibiting tumor cell proliferation, inducing tumor cell differentiation and apoptosis. Among them, Lentinan is a potential drug expected to be used in clinic in the future 51 . (2) Reducing oncogene expression and inhibiting tumor angiogenesis.…”

“…It was found to inhibit the growth of breast cancer and lung cancer, and promoted the proliferation and activation of CD8+ T cells and induced the polarization of TANs toward the N1 phenotype, resulting in an anti-tumor effect. 51 He et al explored the mechanism of Salvia miltiorrhiza Bunge polysaccharides to improve the immune function of rats with gastric cancer. It was found that compared with the gastric cancer model group, Salvia miltiorrhiza Bunge polysaccharides enhanced the killing ability of NK cells and CTLs, increased the expression levels of IL-2, IL-4, IL-10, IgA, IgG and IgM in serum, and decreased the levels of IL-6 and TNF-α, which enhanced the immune function of rats with gastric cancer.…”

Extraction of polysaccharides from Maca enhances the treatment effect of 5-FU by regulating CD4+T cells

“…Polysaccharides are a type of natural active product, and some have been shown to have immunomodulatory and anti-tumor properties. The mode of the anti-tumor activity of polysaccharides is totally two-fold: one way is to kill tumor cells directly such as polysaccharides from Phaeodactylum tricornutum [ 21 ], and the other way is to play a synergistic and attenuating role in chemotherapy such as Lentinan [ 22 ]. Some research has reported that Maca polysaccharides could assist in the treatment of tumors [ 23 , 24 ].…”