2022 World Conference on Lung Cancer (ePosters)-EP16.01-001. Transforming Growth Factor-inhibits Interferon-mediated Immune Resistance in Lung Cancer

EP16.01-001. Transforming Growth Factor-inhibits Interferon-mediated Immune Resistance in Lung Cancer

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Researchers from Tongji Hospital in Wuhan, China, have found that a protein called transforming growth factor-beta (TGF-β1) may inhibit the effectiveness of immune checkpoint blockers (ICBs) in the treatment of lung cancer. Immune checkpoint blockers have been successful in treating lung cancer, but the presence of immunosuppressive elements in the tumor microenvironment can limit their effectiveness. The researchers conducted preclinical studies and clinical trials using a fusion protein called M7824, which is designed to block a protein called PD-L1 and sequester TGF-β1 in the tumor microenvironment. They found promising results in terms of the fusion protein's antitumor effect. However, the researchers note that the role of TGF-β1 in the context of immunotherapy is not well recognized and further investigation is needed. <br /><br />The researchers examined the expression of PD-L1 and IDO1, two immunosuppressive proteins, in lung cancer cell lines and fresh tumor tissues. They found that TGF-β1 significantly inhibited the expression of PD-L1 and IDO1 in response to interferon-gamma (IFN-γ), an important cytokine in immunotherapy. They also discovered that TGF-β1 activated the PI3K-AKT pathway in lung cancer cells, and inhibiting this pathway resulted in downregulation of TGF-β1-induced signaling. Additionally, they found that TGF-β1 inhibited the phosphorylation of JAK1, JAK2, and STAT1, further impacting immune resistance.<br /><br />Based on their findings, the researchers suggest that TGF-β1 signaling may counteract the immune resistance induced by IFN-γ, potentially improving the efficacy of ICBs. They emphasize that their study provides new insights into the complex role of TGF-β1 in immunotherapy.

Asset Subtitle

Ye Fan

Meta Tag

Speaker Ye Fan

Topic Tumour Biology and Biomarkers - Immune Biology & Immunotherapy

Keywords

Tongji Hospital

Wuhan

China

TGF-β1

ICBs

lung cancer

tumor microenvironment

fusion protein

immunotherapy

immune resistance