biostudies-literatureLuan FNIAID NIH HHSe202503335https://www.ebi.ac.uk/biostudies/studies/S-EPMC12559151biostudies-literatureUnknown9(1)T cells are one of the most powerful weapons to fight cancer; however, T-cell exhaustion and dysfunction restrict their long-lasting function in antitumor immunity. B-cell lymphoma 6 (BCL6) has many functions in CD8 T cells; however, it is unclear how it regulates the effector function and exhaustion of CD8 cells. Overall, a low level of BCL6 mRNA in human cancer samples is associated with better outcomes, but high expression of BCL6 is specifically observed in cytotoxic CD8 T cells. We found that BCL6 deficiency in activated CD8 T cells enhanced tumor repression in multiple mouse models. More IL-2-expressing CD8 T cells and reduced proportions of exhausted or dysfunctional CD8 T cells were detected within tumors when <i>Bcl6</i> was knocked out upon T-cell activation. Glycolysis was promoLife science allianceLoss of &lt;i&gt;Bcl6&lt;/i&gt; promotes antitumor immunity by activating glycolysis to rescue CD8 T-cell function.PMC12559151R01 AI137252Blane TRLuan FLi YTran JTHuang ZNemazee DNing JBhargava RXiao CfalseLoss of &lt;i&gt;Bcl6&lt;/i&gt; promotes antitumor immunity by activating glycolysis to rescue CD8 T-cell function.T cells are one of the most powerful weapons to fight cancer; however, T-cell exhaustion and dysfunction restrict their long-lasting function in antitumor immunity. B-cell lymphoma 6 (BCL6) has many functions in CD8 T cells; however, it is unclear how it regulates the effector function and exhaustion of CD8 cells. Overall, a low level of BCL6 mRNA in human cancer samples is associated with better outcomes, but high expression of BCL6 is specifically observed in cytotoxic CD8 T cells. We found that BCL6 deficiency in activated CD8 T cells enhanced tumor repression in multiple mouse models. More IL-2-expressing CD8 T cells and reduced proportions of exhausted or dysfunctional CD8 T cells were detected within tumors when <i>Bcl6</i> was knocked out upon T-cell activation. Glycolysis was promo2026-01-01T00:00:00Z2026 Jan2026-06-05T07:14:20.88Z2026-05-14T03:09:10.433ZS-EPMC125591514114521110.26508/lsa.202503335