A friend in a forest of radiation-immune interactions: BAMBI improves antitumor effects by limiting radioresistance
Sean Sachdev
Sean Sachdev
Published December 15, 2023
Citation Information: J Clin Invest. 2023;133(24):e176061. https://doi.org/10.1172/JCI176061.
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Commentary

A friend in a forest of radiation-immune interactions: BAMBI improves antitumor effects by limiting radioresistance

Abstract

Radiation therapy (RT) remains one of the most effective and utilized oncologic treatments available. While it can directly yield tumor cell death, its impact on the immune microenvironment is more complex, promoting either an antitumor response or, conversely, a tumor-promoting state. TGF-β, induced by RT, yields a more immunosuppressive environment, including potentially blunting response to immune-checkpoint blockade. In this issue of the JCI, Wang and colleagues demonstrate that RT reduced expression of bone morphogenetic protein and activin membrane-bound inhibitor (BAMBI), a TGF-β pseudoreceptor. Limiting this effect, or increasing BAMBI, improved RT-induced tumor cell killing, tumor response, and antitumor immune effects. This realization points to a pathway of potential clinical translation.

Authors

Sean Sachdev

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Figure 1

Targeting BAMBI during or after radiation treatment could improve tumor control.

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Targeting BAMBI during or after radiation treatment could improve tumor ...
While RT can kill tumor cells, it also induces MDSCs to produce TGF-β, resulting in greater MDSC tumor infiltration, more T cell functional suppression, and greater tumor growth. BAMBI serves as a TGF-β pseudoreceptor and limits these effects. In irradiated MDSCs, interaction of YTDF2 results in the degradation of BAMBI mRNA. Following RT, therapeutic manipulation that increases BAMBI or limits its reduction may be key in improving tumor control. This strategy may be especially effective during an often-utilized combination of radiation and immunotherapy.