Tumor Antigen Carcinoembryonic Antigen Inhibits Human CD4 Helper T Cell Activation

Abstract

Carcinoembryonic antigen (CEA) is a well-known tumor antigen. It is found in serum of various cancers including colorectal carcinoma, gastric carcinoma. Uncontrolled level of CEA in individuals increases the risk of recurrence and metastasis. In this study we show that CEA can directly inhibit human PBMC derived CD4+ T cell activation. When cultured with plate-bound human recombinant CEA under anti-CD3, CD28 stimulation, CD4+ T cells showed decreased proliferation and cytokine production. Soluble form of CEA did not show such effect. Following stimulation the level of CD69, phosphorylated ZAP70, phosphorylated ERK was decreased in CEA treated CD4+ T cells as early as 4 hours post stimulation. When treated with SHP inhibitor (NSC-87877) proliferation was restored, showing that the inhibitory effect was mediated by SHP. To show the physiological relevance of CEA mediated inhibition, we used CEA overexpressing murine colon adenocarcinoma cell line (MC38-CEA) and co-cultured it with human CD4+ T cells. As expected, CD4+ T cells cultured with MC38-CEA showed decreased proliferation but those cultured with MC38 did not. This suggests that impaired T cell response mediated by CEA can be a possible mechanism of tumor evasion.