ESR2 and neoplasm: The antitumor effect of S-equol observed in the current study, either alone or in combination with αPD-1, is consistent with a recent report of another ERβ agonist LY500307 in overcoming tumor resistance to ICB immunotherapy.6 Given both tumor-intrinsic and -extrinsic antitumor activities of ERβ, the underlying mechanism by which S-equol inhibits tumor growth could be multifactorial and merits further investigation.