The adaptation model of immunity: tumor cell adaptation to tumor-reactive immune responses

Abstract Tumor cells are genetically unstable carrying continuously changing mutations which the basis for neoantigen vaccines. Pre-existing immune responses against tumor-associated self-antigens as well semi-nonself neoantigens have been reported in cancer patients. These data self-nonself (SNS) model of immunity, proposing that tumor expressing induce tolerance. The adaptation proposes expression many receptors (AdRs) linked to anti-apoptotic pathways cells, one is be B7-H1, responsible survival presence anti-tumor responses. To this end, efficacy checkpoint inhibitors mainly because blockade pathway downstream B7-H1. Limited these therapies several AdRs may expressed by compensate In fact, B7-H1 mischaracterized PD-L1 ligand while it a bi-directional receptor relays signal both trans, when engaged with PD-1 on T and cis, or B7.1 DCs cells. could also exist dual system consisting those pathways, i.e., TNFR2, countered pro-apoptotic i.e. TNFR1. outcomes tumor-reactive cell would depend presence/absence balance between an AdR its counter-receptor Therefore, current immunotherapies should focus discovery inhibition AdRs, knocking out nominal AdLs tumor-specific This work was supported Office Assistant Secretary Defense Health Affairs through Breast Cancer Research Program under Award No. W81XWH2210793. Opinions, interpretations, conclusions, recommendations authors not necessarily endorsed U.S. Department Defense. multi-investigator pilot funding from VCU Massey Centre, part NIH/NCI Centre support grants P30 CA016059.