Interestingly, higher CD4+ infiltration was associated with higher tumor stage and lymph node spread and also improved overall survival in patients with stage I-III non-small cell lung cancer (NSCLC) (22).Together with our results, these findings could indicate that increased CD4+ T-lymphocytes may be associated with tumors of lower T stage, decreased invasiveness, and less aggressive disease, perhaps by means of E2 and ERbeta on CD4+ T cells in the TME (16, 17). Here, ESR2 is linked to neoplasm.