Inactivated mycobacteria stimulation potentiates macrophage shifting to proinflammatory phenotype in lung cancer patients

Abstract

Local administration of attenuated Mycobacterium has been used as a cancer treatment adjuvant to re-boost patient immune responses with variable clinical outcomes. We aimed to clarify the impact of inactivated mycobacterial components on macrophages from patients with lung cancer, which play critical roles in shaping immunological regulation in the tumor microenvironment. Peripheral blood macrophages were
collected from lung cancer patients and healthy subjects and then stimulated with inactivated Mycobacterium components to observe phenotypic changes. Macrophage phenotype was characterized by flow cytometry analysis, and cytokine assays were used to determine the inflammatory profile. We found that inactivated mycobacteria stimulation upregulated the CD86+ pro-inflammatory macrophage population in
both healthy subjects and lung cancer patients. Cytokine analysis further supported the findings by showing elevated pro-inflammatory TNFα, IL1β, and IFNγ secretion. Macrophages from lung cancer patients distinctly revealed subsequent increases in anti-inflammatory cytokines including IL-10 and TGF-β, however IL-4 was significantly diminished. Tumor cells have been known to alter recognition and elimination
by macrophage and rather imposed its function to promote tumor growth and dissemination. Promotion of macrophages toward a pro-inflammatory phenotype is expected to rewire its anti-tumoral functions. Our study provides a novel insight on revealing molecular alterations of inactivated mycobacteria-reeducated macrophages from lung cancer patients, which should help illuminate potential strategies of inactivated mycobacteria-stimulated macrophage-based combination therapy for cancer treatment.