In a multivariate cox regression analysis using age, sex, lesion site, tumor size, histological grade, CD4+ TILs, CD8+ TILs, MHC I, MHC II, and COPB2 as co-factors, larger tumor size (odds ratio [OR]= 4.812, 95% confidence interval [CI]= 1.025–22.588; p = 0.046, poorly differentiated histologic grade (OR = 13.576; 95% CI = 1.151–160.104; p = 0.038), and high COPB2 expression (OR = 10.905; 95% CI = 1.714–69.372; p = 0.011) had an independent impact on the worsened recurrence-free survival of cSCC patients (Table 3). This evidence concerns the gene CD4 and skin squamous cell carcinoma.