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Ira Mellman1 paints rosy prospects for cancer immunotherapy, if only the field receives more support. We?ve repeatedly heard such promises over the past 40 years. Yet despite continuing strong support, progress has been minimal and I expect it will be so in the future. To be effective, cancer immunotherapy requires that cancer cells have antigens on their surface (i) different than on normal cells and, (ii) constantly expressed during the cell cycle and essential for cell survival. Both requirements are mutually inclusive. If cancer-specific antigen(s) are not essential for cell survival, cancer resistance to immunotherapy by antigen shedding or downregulation of its synthesis will evolve during the treatment. To shed or not express a particular antigen is mechanistically simpler and thus more likely to occur compared with mechanisms that generate resistance to chemotherapy, such as ...
