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Background Checkpoint inhibitors have emerged as a standard of care therapy for non-small cell lung cancer (NSCLC). Mutations in STK11 occur in 20% of NSCLC and are associated with poor responsiveness to anti-PD-1 agents, creating an increased need to identify novel therapeutic targets for this tumor subtype.Methods Functional genomic screening utilizing CRISPR-Cas9 is a powerful tool to identify new therapeutic targets in cancer. We applied this technology specifically to STK11-mutant syngeneic tumor models in mice to identify targets which restore sensitivity to anti-PD-1 therapy.Results Knockout of MGAT1, an enzyme critical for maturation of high-mannose N-glycans into hybrid and complex glycan types, was able to reverse STK11-mutant-driven resistance to anti-PD-1 treatment. Parallel in vitro screens using co-culture systems showed that disruption of N-glycosylation was also a powerful mechanism in sensitizing tumor cells to direct killing by antigen-matched CD8 T cells. Our investigation suggests that global disruption of N-glycans likely impacts the ability of T cells to recognize tumor cells. The role of MGAT1 in immune evasion was dependent on its enzymatic activity, making it a promising target for therapeutic small molecule inhibitor development.Conclusions Our work implicates N-glycosylation as a key mediator of immune evasion in STK11 mutant NSCLC and nominates MGAT1 a novel target for therapeutic development to overcome this mechanism.