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Over 90% of PDAC have oncogenic KRAS mutations, and phosphoinositide 3-kinases (PI3Ks) are direct effectors of KRAS. Our previous study demonstrated that ablation of\n                    <jats:italic>Pik3ca<\/jats:italic>\n                    in KPC (\n                    <jats:italic>Kras<\/jats:italic>\n                    <jats:sup>G12D<\/jats:sup>\n                    ;\n                    <jats:italic>Trp53<\/jats:italic>\n                    <jats:sup>R172H<\/jats:sup>\n                    ;\n                    <jats:italic>Pdx1-Cre<\/jats:italic>\n                    ) pancreatic cancer cells induced host T cells to infiltrate and completely eliminate the tumors in a syngeneic orthotopic implantation mouse model. Now, we show that implantation of\n                    <jats:italic>Pik3ca<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    KPC (named \u03b1KO) cancer cells induces clonal enrichment of cytotoxic T cells infiltrating the pancreatic tumors. To identify potential molecules that can regulate the activity of these anti-tumor T cells, we conducted an in vivo genome-wide gene-deletion screen using \u03b1KO cells implanted in the mouse pancreas. The result shows that deletion of propionyl-CoA carboxylase subunit B gene (\n                    <jats:italic>Pccb<\/jats:italic>\n                    ) in \u03b1KO cells (named p-\u03b1KO) leads to immune evasion, tumor progression, and death of host mice. Surprisingly, p-\u03b1KO tumors are still infiltrated with clonally enriched CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells but they are inactive against tumor cells. However, blockade of PD-L1\/PD1 interaction reactivated these clonally enriched T cells infiltrating p-\u03b1KO tumors, leading to slower tumor progression and improve survival of host mice. These results indicate that\n                    <jats:italic>Pccb<\/jats:italic>\n                    can modulate the activity of cytotoxic T cells infiltrating some pancreatic cancers and this understanding may lead to improvement in immunotherapy for this difficult-to-treat cancer.\n                  <\/jats:p>","DOI":"10.7554\/elife.96925","type":"journal-article","created":{"date-parts":[[2024,4,22]],"date-time":"2024-04-22T09:25:09Z","timestamp":1713777909000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.96925","source":"Crossref","is-referenced-by-count":5,"title":["Propionyl-CoA carboxylase subunit B regulates anti-tumor T cells in a pancreatic cancer mouse model"],"prefix":"10.7554","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-0788-3019","authenticated-orcid":true,"given":"Han V","family":"Han","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05qghxh33","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Physiology and 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