TNF and neoplasm: The high level of Ifnγ and Tnfα act as bidirectional roles in the formation of the TME.51-53 The Ccl2 and Ccl5 are always regarded as suppressive chemokines which are involved in the formation of the TME.54,55 On the other hand, a decrease of Il6 and Il8 in the tumor microenvironment is beneficial for the suppression of tumor proliferation.56 Nevertheless, these differences gradually reduced when the solid adenocarcinoma formed (Supplementary Figure S4E).