A loss of BCATc from T cells does not induce an overreactive immune response to monoclonal anti-CTLA4 therapy in mice challenged with EL-4 lymphoma
Description
The anti-CTLA4 drug, Ipilimumab, is used to treat melanoma and other cancers. Immune-related adverse effects include gastrointestinal, dermatologic, and hepatic disturbances. Both humans and mice show gut inflammation, liver toxicity, and dermatologic issues due to T-cell hyperactivation. The cytosolic branched-chain aminotransferase (BCATc) is overexpressed in cancer and proposed as an immunosuppressive enzyme. In this study, we assessed whether a loss of BCATc from mouse T cells, in combination with anti-CTLA4 therapy, may cause side effects. Mice with T cells deficient in BCATc (T-BCATcKO) were challenged with 2.5x10^5 mouse EL-4 lymphoma followed by i.e. injection of anti-CTLA4, or an isotope, on days 2,5, and 10. Body weight, tumor weight, and food intake were recorded every day, followed by organ collection on day 15. Intestines were screened for markers of inflammation, such as the tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ), using RT-PCR.
Results showed no statistically significant differences in body weight, food intake, or the organ weights (or organomegaly) when hearts, lungs, kidneys, intestines, spleens, thymus, brains, or livers were compared to those of controls' littermates. Likewise, no significant changes in the mRNA expression levels of TNF-α and IFN-γ were observed between the different experimental groups. This suggests that a loss of BCATc from T cells does not induce inflammation and is a suitable target for pharmacological inhibition in follow-up oncological studies. By further understanding T cell metabolism in relation to immunotherapy responses in anti-tumor immunity, research can lead to more personalized cancer treatments.
Citation Information
Kotula, Anna; Fagan, Madison; Wetzel, Tanner; Kelm, Tanner; and Ananieva-Stoyanova, Elitsa, "A loss of BCATc from T cells does not induce an overreactive immune response to monoclonal anti-CTLA4 therapy in mice challenged with EL-4 lymphoma" (2026). Office of Research DMU Research Symposium. 77.
https://digitalcommons.dmu.edu/researchsymposium/2025rs/2025abstracts/77
A loss of BCATc from T cells does not induce an overreactive immune response to monoclonal anti-CTLA4 therapy in mice challenged with EL-4 lymphoma
The anti-CTLA4 drug, Ipilimumab, is used to treat melanoma and other cancers. Immune-related adverse effects include gastrointestinal, dermatologic, and hepatic disturbances. Both humans and mice show gut inflammation, liver toxicity, and dermatologic issues due to T-cell hyperactivation. The cytosolic branched-chain aminotransferase (BCATc) is overexpressed in cancer and proposed as an immunosuppressive enzyme. In this study, we assessed whether a loss of BCATc from mouse T cells, in combination with anti-CTLA4 therapy, may cause side effects. Mice with T cells deficient in BCATc (T-BCATcKO) were challenged with 2.5x10^5 mouse EL-4 lymphoma followed by i.e. injection of anti-CTLA4, or an isotope, on days 2,5, and 10. Body weight, tumor weight, and food intake were recorded every day, followed by organ collection on day 15. Intestines were screened for markers of inflammation, such as the tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ), using RT-PCR.
Results showed no statistically significant differences in body weight, food intake, or the organ weights (or organomegaly) when hearts, lungs, kidneys, intestines, spleens, thymus, brains, or livers were compared to those of controls' littermates. Likewise, no significant changes in the mRNA expression levels of TNF-α and IFN-γ were observed between the different experimental groups. This suggests that a loss of BCATc from T cells does not induce inflammation and is a suitable target for pharmacological inhibition in follow-up oncological studies. By further understanding T cell metabolism in relation to immunotherapy responses in anti-tumor immunity, research can lead to more personalized cancer treatments.
