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Cancer-testis antigens (CTAs) are tumor antigens normally expressed in the testes but are aberrantly expressed in several cancers. Overexpression of CTAs has been shown to drive cancer metastasis. R.J. Seager, Sarabjot Pabla, and our Labcorp team evaluated patients with advanced NSCLC, treated with chemoimmunotherapy or immunotherapy alone, who underwent comprehensive genomic and immune profiling. Patients with a high CTA burden score and were treated with immunotherapy had improved overall survival compared to those with low CTA burden score. There was significant co-expression of CTAB with tumor mutational burden, however, not with PD-L1. CTA burden is a potential biomarker of immunotherapy response and warrants further exploration.