Based on these observations, we advance a testable working hypothesis: in EGFR-mutant NSCLC, TP53 or KRAS co-mutation may partially mitigate the “immune-cold” phenotype, thereby enhancing sensitivity to immunotherapy; however, given that pivotal trials such as CheckMate 722 and KEYNOTE-789 did not meet their prespecified primary endpoints (30), this should be regarded as hypothesis-generating rather than confirmatory and requires validation in functional studies and prospective trials. The gene discussed is TP53; the disease is non-small cell lung carcinoma.