Furthermore, our data exhibits that Cdk2-/- cancer cells treated with MTX trigger a more robust immunostimulatory responses than WT cells, including apoptosis stress response, surface calreticulin expression, endoplasmic reticulum stress response, HMGB1 (High Mobility Group Box 1) release, and type-1 interferon response. The gene discussed is HMGB1; the disease is cancer.