Background  Cancer patients with concomitant anemia have a poorer prognosis, and the mechanism by which anemia exerts a pro-tumor effect is not yet clear.

Objective  The effects of anemia on anti-tumor immune cells and immunosuppressive cells in peripheral blood mononuclear cells (PBMC), spleen and tumor tissues of tumor-bearing mice were observed.

Methods  The mice in this study were randomly divided into three groups: healthy,control and anemic groups. The percentage of T lymphocytes and natural killer cells (NK cells) and changes in immunocompetence in spleen and tumor tissues were detected by flow cytometry. The cell abundance of erythroid progenitor cells (EPCs) and myeloid-derived suppressor cells (MDSCs) in peripheral blood, spleen and tumor tissues were detected. Tumor tissues were collected from each group and gene expression differences between the anemic and control groups were detected by transcriptome sequencing (RNA sequencing, RNA-seq).

Results  Flow cytometry results showed that the proportion of T cells and NK cells in the spleens of the control group was lower than that of the healthy group (P<0.05), and the proportion of T cells in the spleens of the anemic group was lower than that of the control group (P< 0.05). The secretion of TNF-α and IFN-γ by CD4 ⁺ T cells and NK cells as well as the secretion of IFN-γ by CD8 ⁺ T cells was increased in the spleens of the control group (P< 0.01), and anemia inhibited the activation of T cells and NK cells in the spleens. In addition, anemia decreased tumor infiltration by CD4 ⁺ T cells (P<0.01) and increased CD8 ⁺ T cells and NK cells (P<0.01). Anemia inhibited TNF-α secretion by CD4 ⁺ and CD8 ⁺ T cells in tumor tissues (P<0.01), and also inhibited IFN-γ secretion by CD4 ⁺ T cells and NK cells (P<0.05). In addition, CD45 ⁺ EPCs in spleen, PBMC and tumor tissues of the anemic group were higher than those in the control group (P<0.01), and CD45 ⁺ EPCs in tumor tissues of mice in the anemic group could secrete ARG1 and IFN-γ. Anemia increased the proportion of MDSCs in spleen and tumor tissues (P<0.01). rna-seq analyses showed that anemia reduced the number of M0 type macrophages and activated NK cells infiltration, increased initial M2 type macrophages and TH2 cells infiltration; and upregulated the TNF-αsignaling pathway and NOD-like receptor signaling pathway.

Conclusion  Anemia may promote tumors by inhibiting the anti-tumor immune response of T lymphocytes.