CD4 and neoplasm: One of our earliest observations was that the adoptive transfer of large numbers of mesothelioma-specific T cells, CD4 and/or CD8, did not result in eradication of an established tumor (Marzo et al., 1999a), raising concerns for us that any such therapy alone, such as modern CAR-T-cell therapy, may not be effective in solid tumors unless the obstacles of effector site resistance to immune attack could be overcome, something being studied in a number of centers.