2022 World Conference on Lung Cancer (ePosters)-EP16.01-027. MIF ImprovesImmune Microenvironmentof Lewis Lung Cancer Brain Metastases after Radiotherapy ViaReducing M2 Macrophages

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Researchers from Union Hospital at Tongji Medical College in China have found that inhibiting macrophage migration inhibitory factor (MIF) can improve the immune microenvironment in brain metastases of Lewis lung cancer after radiotherapy. Previous studies have shown that inhibiting the MIF/CD74 signaling pathway can transform intracranial macrophages from M2 to M1 type after radiotherapy, leading to radiosensitization in brain metastases. M2 macrophages are known to be components of tumor immunosuppression microenvironment, and they play a role in decomposing arginine, which is essential for the growth and development of T cells. The researchers focused on understanding the mechanism of MIF regulating tumor infiltrating lymphocytes (TILs) by inducing macrophage phenotype transformation.<br /><br />To test their hypothesis, the researchers used MIF-knockdown Lewis cells and conducted experiments on mice with lung cancer brain metastases. Their results showed that MIF knockdown combined with whole brain irradiation increased the expression of M1-type markers (such as iNOS) and reduced the expression of M2-type markers (such as Arg-1), indicating the promotion of M1 phenotype and reduction of M2 phenotype. Additionally, the combination of MIF knockdown and irradiation increased the proportion of CD8T/CD4T and CD8IFN-γT/CD4Foxp3T cells, suggesting an increase in TILs. The researchers also observed that inhibiting MIF enhanced the shrinkage of tumors induced by irradiation.<br /><br />The researchers further found that the downregulation of MIF expression combined with irradiation promoted T cell infiltration and inhibited tumor growth through the mediation of macrophages. They also observed an increase in arginine content after irradiation or MIF knockdown, indicating that reducing M2-type macrophages could lead to an increase in arginine content. The addition of exogenous arginine also increased the CD8/CD4TILs ratio and inhibited tumor growth.<br /><br />In conclusion, inhibiting MIF expression can reduce the expression of Arg-1 from M2-type macrophages, increase arginine content, promote TIL infiltration, and enhance the efficacy of radiotherapy in brain metastases. This research highlights the potential of targeting MIF in improving the immune microenvironment and sensitizing tumors to radiotherapy.

Asset Subtitle

Xiaorong Dong

Meta Tag

Speaker Xiaorong Dong

Topic Tumour Biology and Biomarkers - Immune Biology & Immunotherapy

Keywords

macrophage migration inhibitory factor

MIF

immune microenvironment

brain metastases

Lewis lung cancer

radiotherapy

M2 macrophages

tumor immunosuppression

tumor infiltrating lymphocytes

arginine content