Decreased expression of the MHC class I surface antigens by down regulation of molecules such as TAP1 or TAP2 of the antigen processing machinery (APM) is a mechanism used by the cancers including esophageal adenocarcinomas (EAC) to escape from immune surveillance (Milano F. et al, 2010). Earlier we discovered that down-regulation of TAP2 in the EAC cell line OE19, accounts for a deficient anti-tumor T cell response. We found that IFNγ restored TAP2 expression in OE19 and restored the sensitivity of these cells to T cell induced cytotoxicity. OE33, another EAC cell line, is sensitive to T cell induced cytotoxicity and has normal expression of TAP2. However siRNA mediated silencing of TAP2 in OE33 resulted in a significantly decreased T cell induced cytotoxicity. Here we further evaluated molecular mechanisms which may be at the base of these APM impairments. Since microRNAs are known as pivotal post-transcriptional regulators and players in the regulation of cancer and the immune system, we analyzed the expression pattern of 88 microRNAs, which are differentially expressed during physiological and pathological immune responses, in the above mentioned cell lines by qPCR arrays. We found a significant differential expression profile of microRNAs in OE33 and OE19 cell lines. More specifically we found that seven of the microRNAs which had significantly lower expression levels in OE33 could be downregulated in OE19 through IFN-γ treatment. By using different computational tools for the prediction of the seven candidates microRNA targets, we found that one of the most significantly down-regulated microRNAs, can directly target the TAP2 3'UTR mRNA sequence and can inhibit the transcription of this protein at a post-transcriptional level. Further investigations on microRNA mediated post-transcriptional modifications of the APM pathway can lead to the discovery of novel targets to circumvent APM-related immune escape mechanisms in solid tumors.