Tumor-regulated macrophage type 2 differentiation promotes immunosuppression in laryngeal squamous cell carcinoma

Aims: Tumor-associated macrophage (TAM) residing in tumor microenvironment as the major niche cell made remarkable contribution to tumor growth. However, the functional role of macrophage and its different differentiating state as well as the regulating mechanism in laryngeal squamous cell carcinoma (LSCC) remains not fully clear. Materials and methods: LSCC samples were collected from patients. Human peripheral blood mononuclear cells (PBMC) were collected from volunteers' blood, and used for macrophage induction. Enzyme-Linked Immuno-sorbent Assay (ELISA) was performed to detect proinflammatory cytokines. Immunostaining was prepared to observe tumor tissues. Key findings: Here, we found the number of type 2 macrophage (M Phi 2) and PDL-1 expression was increased in LSCC that was correlated with poor prognosis in patients with LSCC. Tumor cells induced macrophage into type 2 differentiation by TGF-beta/Smad3 signaling. The primed M Phi 2 produced IL-10 by activating JAK/STAT signaling that promoted PDL-1 expression in tumor cells leading to its immunosuppression. Inhibition of JAK/STAT signaling promoted tumor cells death from immune cells killing by regulating PDL-1 expression. Targeting cytokines TGF-beta or IL-10 synergistically enhances the sensitivity of tumors to chemotherapy in vivo. Significance: In conclusion, our findings showed tumor cells and M Phi 2 were bilaterally regulated through cytokines production that integrally advanced tumor progression through boosting anti-tumor immunity. It provides insight to develop immune strategies synergy with chemotherapy in treating laryngeal squamous cell carcinoma.

Automated summary

The study revealed an increase in type 2 macrophages and PDL-1 expression in laryngeal squamous cell carcinoma (LSCC), correlating with poor prognosis. Tumor cells induced macrophages into type 2 differentiation through TGF-beta/Smad3 signaling, leading to immunosuppression. Inhibition of JAK/STAT signaling enhanced tumor cell sensitivity to immune cell killing by regulating PDL-1 expression. Targeting TGF-beta or IL-10 could synergistically enhance sensitivity to chemotherapy in tumors.