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.

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Symbolic interactionism is within the positivist school of thought. Using a social psychological vantage point, symbolic interactionism—as explained by members of the Chicago school, specifically by Mead and Thomas—posits that one's self‐concept and behavior change from one situation to another. This change depends on the subjects' interpretation of symbols from a given situation and on their generalized interpretation of symbols communicated by others. Symbolic interactionism is often thought of as one of America's main contributions to theory; this theoretical perspective has continued to be popular nearly 100 years after its development around 1914. Some theories shaped by symbolic interactionism include social learning, labeling, and violentization theories. The idea that social reality is fluid, always being re‐created and appearing in new situations is currently very relevant; in consequence, theoretical developments using aspects of symbolic interactionism are likely to continue for some time into the future.

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