To confirm these results, we performed an unsupervised analysis using CITRUS among HD, BC before, and after chemotherapy groups, which revealed a statistically significant increase in a cluster characterized by an exhaustion central memory CD4 phenotype in BC patients before chemotherapy (199977: CD3+ CD4+ CD62L+ CD45RO+ TIM3+ LAG3+; Fig 5A, 5B and 5D). The gene discussed is HAVCR2; the disease is breast cancer.