Compositions, methods and uses of genetically modified NKT cells to induce an NKT cell immune response against tumor or to change a microenvironment of the tumor by suppressing an activity of myeloid-derived suppressor cells are presented. In some embodiments, naive NKT cells are obtained from a patient having a tumor, and are genetically engineered to include a chimeric protein, a T cell receptor, a hybrid T cell receptor replacing the endogenous T cell receptor, or one of CD40L and Fas-L. The naive or genetically modified NKT cells can be administered to a cancer patient to trigger and/or boost immune response against the tumor.
