biostudies-literatureUnknown649(8096)Virassamy BParity and breastfeeding reduce the risk of breast cancer, particularly triple-negative breast cancer (TNBC)^1,2, yet the immunological mechanisms underlying this protection remain unclear. Here we show that parity is associated with increased numbers of CD8⁺ T cells, including cells with a tissue-resident-memory-like phenotype within human normal breast tissue. In mouse models, pregnancy followed by lactation and involution drove the accumulation of CD8⁺ T cells in the mammary gland, coinciding with reduced tumour growth and increased intratumoural immune cell infiltration, effects that were abrogated by CD8⁺ T cell depletion. Importantly, this CD8⁺ T-cell-dependent tumour control was observed only after a complete cycle of lactation aNature449-459https://www.ebi.ac.uk/biostudies/studies/S-EPMC12779547biostudies-literatureParity and lactation induce T-cell-mediated breast cancer protection.PMC12779547Flanagan JBodek SVisvader JPatterson BTaylor RSpurdle AZaheed MSkandarajah APoliness CTaylor JJames PTrainer AFenton GSexton ADixon JKoehler JCummings MEdwards SWalker LJana MNeeson PJDickson RHayward NFox SPang JMBurn TNMeiser BRamus SMarsh DBeesley JCourtney EAntill YVirassamy BO'Sullivan SWilliams RCao MGeorge PHarraka PLee JRagunathan AHarris MAdeFazio AKollias JAndrews LThorne HKirk JShaw Jvan Geelen CTBuckley MJenkins MPachter NButow PCohen PKay JField MCaramia FSalisbury ESaunus JCui JAw Yeang HXPieper ERickard EClarke KSrinivasa SFriedlander MGaff CSimpson PMann GLobb LLippey JSavas PLakhani SSaleh MChauhan MChakrabarti ABrown EAmor DWang JChauhan DDawson SJPearn ASaunders CWinship IHunt CNightingale SBurke JLindeman GChenevix-Trench GBallan JDGreening SCrook AO'Connell SShelling AMcLachlan SAkConFab consortiumTeo SHDarcy PKDelatycki MLi SFarshid GChallice DJLoi SYoung MABrennan MForrest LScott CSpeed TPFrench JSant SMilne RColley AFong PLipton LO'Malley MMRHoskins CLara Gonzalez LEBotes LScott RPan JWMackay LKHopper JFellows AHarris MPhillips KHun MChristian APathak GHart SBennett IBogwitz MSouthey MCaldon LGattas MLawrence MKidd ACampbell IGallego-Ortega DBrown MSalgado RRobinson BIdrizi RBalleine RTucker KfalseParity and lactation induce T-cell-mediated breast cancer protection.Parity and breastfeeding reduce the risk of breast cancer, particularly triple-negative breast cancer (TNBC)^1,2, yet the immunological mechanisms underlying this protection remain unclear. Here we show that parity is associated with increased numbers of CD8⁺ T cells, including cells with a tissue-resident-memory-like phenotype within human normal breast tissue. In mouse models, pregnancy followed by lactation and involution drove the accumulation of CD8⁺ T cells in the mammary gland, coinciding with reduced tumour growth and increased intratumoural immune cell infiltration, effects that were abrogated by CD8⁺ T cell depletion. Importantly, this CD8⁺ T-cell-dependent tumour control was observed only after a complete cycle of lactation a2026-01-01T00:00:00Z2026 Jan2026-06-06T20:02:19.614Z2026-06-04T03:12:59.203ZS-EPMC127795474111545310.1038/s41586-025-09713-5