Immune checkpoint blockades, or ICBs, have revolutionized treatment for various advanced cancers. However, their effectiveness has plateaued due to therapeutic resistance that renders tumor-infiltrating lymphocytes, or TILs, ineffective. Thus, finding ways to disarm that resistance and rejuvenate anti-cancer TILs—so they can kill tumor cells—is an important goal for cancer clinicians. Yet any potential intervention has to take place under unusual conditions—the cancer microenvironment nearly devoid of oxygen due to fast growth of a tumor and the poor oxygen delivery by the abnormal tumor vasculature.
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