We use integrated preclinial and clinical investigations to determine the contribution of the tumor reprogramed immune microenvironments in lung cancer and breast cancer. We are investigating modalities including subablative radiation and agents that target T cell dysfunction, endoplasmic stress as potent immunomodulators to enhance to the efficacy of immune checkpoint inhibitors. Our goals are to elucidate mechanistic insights into combination treatment, identify cellular and molecular biomarkers that predict major pathologic responders from non-responders, and identify clinically relevant targets for developing novel immunotherapies.