Human tumors tend to activate the immune system regulatory checkpoints as a means of escaping immunosurveillance. For instance, interaction between program death-1(PD-1) and program death-ligand 1(PD-L1) will lead the activated T cell to a state of anergy. PD-L1 is upregulated on a wide range of cancer cells. Anti-PD-1 and anti-PD-L1 monoclonal antibodies(m Abs), called immune checkpoint inhibitors(ICIs), have consequently been designed to restore T cell activity. Accumulating data are in favor of an association between PD-L1 expression in tumors and response to treatment. A PD-L1 expression is present in 30% to 50% of digestive cancers. Multiple anti-PD-1(nivolumab, pembrolizumab) and anti-PD-L1 m Abs(MPDL3280A, Medi4736) are under evaluation in digestive cancers. Preliminary results in metastatic gastric cancer with pembrolizumab are highly promising and phase Ⅱ will start soon. In metastatic colorectal cancer(CRC), a phase Ⅲ trial of MPDL3280 A as maintenance therapy will shortly be initiated. Trials are also ongoing in metastatic CRC with high immune T cell infiltration(i.e., microsatellite instability). Major challenges are ahead in order to determine how, when and for which patients we should use these ICIs. New radiologic criteria to evaluate tumor response to ICIs are awaiting prospective validation. The optimal therapeutic sequence and association with cytotoxic chemotherapy needs to be established. Finally, biomarker identification will be crucial to selection ofpatients likely to benefit from ICIs. For example, interaction between program death-1 (PD-1) and program death-ligand 1 (PD-L1) will lead the activated T cell to a Anti-PD-1 and anti-PD-L1 monoclonal antibodies (m Abs), called immune checkpoint inhibitors (ICIs), have been designed to restore T Accumulation data are in favor of an association between PD-L1 expression in tumors and response to treatment. Multiplex PD-1 (nivolumab, pembrolizumab ) and anti-PD-L1 m Abs (MPDL3280A, Medi4736) are under evaluation in digestive cancers. Preliminary results in metastatic gastric cancer with pembrolizumab are highly promising and phase II will start soon. In metastatic colorectal cancer (CRC), a phase III trial of MPDL3280 A as maintenance therapy will shortl Trials are also ongoing in metastatic CRC with high immune T cell infiltration (ie, microsatellite instability). Major challenges are ahead in order to determine how, when and for who patients we should use these ICIs. New radiologic criteria to evaluate The optimal therapeutic sequence and association with cytotoxic chemotherapy needs to be established. Finally, biomarker identification will be crucial to selection of patients likely to benefit from ICIs.