Saprophytic fungus (Ganoderma sessile) restrained Treg recruitment in the tumor microenvironment by down-regulating CCL28/CCR10 pathway

Ganoderma sessile, a saprophytic fungus, is a traditional Chinese medicinal material used in Chinese folk medicine and cuisine for its potential to enhance cancer patients immunity in clinical practice. However, the underlying mechanisms of its therapeutic effects remain elusive. Therefore, we explored the edible value to determine the underlying mechanisms of GS through multiple breast cancer models. GS was found to suppress tumor growth and lung metastasis, and prolong survival after surgery. It significantly increased tumor-infiltrating CD44^HiCD62L^HiCD8⁺ T_CM cells while decreasing CD4⁺CD25⁺CD127⁻ Treg cells in both lymph nodes and tumors. The mechanism behind GS’s effects primarily involved modulation of the Hif1-a/CCL28 pathway associated with Treg recruitment. Furthermore, GS could reduce CCR10 levels on the surface of Tregs. Collectively, GS inhibits tumor growth and pulmonary metastasis by restraining Treg recruitment through downregulation of the CCL28/CCR10 pathway—a finding which highlights its potential as a natural anti-tumor immune agent warranting further exploration.