The immuno-oncology field reveals promising advancements in tumor microenvironment modulation and therapy. Studies identify boosting cytotoxic T cell activity by reprogramming regulatory T cells expressing specific FOXP3 variants to overcome tumor immunosuppression. New mechanisms highlight MondoA-TXNIP pathway’s role in enhancing antitumor immunity by mitigating lactic acid induced immunosuppression. Additionally, targeted therapies for rare T-cell lymphomas and novel strategies to inhibit spermine metabolism show potential to elevate pancreatic and hematological cancer treatment outcomes.