biostudies-literatureLuoma AMNCI NIH HHS2918-2935.e29https://www.ebi.ac.uk/biostudies/studies/S-EPMC9508682biostudies-literatureUnknown185(16)Neoadjuvant immune checkpoint blockade has shown promising clinical activity. Here, we characterized early kinetics in tumor-infiltrating and circulating immune cells in oral cancer patients treated with neoadjuvant anti-PD-1 or anti-PD-1/CTLA-4 in a clinical trial (NCT02919683). Tumor-infiltrating CD8 T cells that clonally expanded during immunotherapy expressed elevated tissue-resident memory and cytotoxicity programs, which were already active prior to therapy, supporting the capacity for rapid response. Systematic target discovery revealed that treatment-expanded tumor T cell clones in responding patients recognized several self-antigens, including the cancer-specific antigen MAGEA1. Treatment also induced a systemic immune response characterized by expansion of activated T cells enricCellTissue-resident memory and circulating T cells are early responders to pre-surgical cancer immunotherapy.PMC9508682T32 CA207021R01 CA173750R01 CA238039R01 CA234018R01 CA251599Rozenblatt-Rosen OGurer CAshenberg OSchoenfeld JDSuo SFerretti APGunasti LMacBeath GHaddad RIWucherpfennig KWNabilsi NRegev ADionne DTadros JVan Allen EMRicker CALuoma AMChen YHUppaluri RPorter CBMLiao SCriscitiello SWang YfalseTissue-resident memory and circulating T cells are early responders to pre-surgical cancer immunotherapy.Neoadjuvant immune checkpoint blockade has shown promising clinical activity. Here, we characterized early kinetics in tumor-infiltrating and circulating immune cells in oral cancer patients treated with neoadjuvant anti-PD-1 or anti-PD-1/CTLA-4 in a clinical trial (NCT02919683). Tumor-infiltrating CD8 T cells that clonally expanded during immunotherapy expressed elevated tissue-resident memory and cytotoxicity programs, which were already active prior to therapy, supporting the capacity for rapid response. Systematic target discovery revealed that treatment-expanded tumor T cell clones in responding patients recognized several self-antigens, including the cancer-specific antigen MAGEA1. Treatment also induced a systemic immune response characterized by expansion of activated T cells enric2022-01-01T00:00:00Z2022 Aug2025-04-04T20:28:42.114Z2025-04-04T20:28:42.114ZS-EPMC95086823580326010.1016/j.cell.2022.06.018