CD28 expression on CD39+ CD4+ T cells was positively correlated to lung squamous cell carcinoma (LUSC) risk (OR, 1.0335 [95% CI, 1.009–1.0586]), inversely mediated by IL-16 (95% CI, −0.01 to −0.0003). The gene discussed is IL16; the disease is squamous cell lung carcinoma.