Host Response to Tumors

Cellular Immunity
The importance of lymphoid cells in tumor immunity has been repeatedly shown in animal experiments. The T cell is the primary cell thought to be responsible for direct recognition and killing of tumor cells. T cells carry out an immunologic surveillance, destroying newly transformed tumor cells after recognizing TAAs. In humans, specific T-cell clones can be grown, which recognize and directly kill autologous tumor cells. T cells are uniquely capable of killing cells expressing TAA intracellularly because peptide fragments derived from these intracellular proteins can be bound to class I MHC antigens on the tumor cell surface, which can be recognized by cell-surface T-cell receptors. Thus, antigens recognized by cytotoxic T-lymphocytes (CTLs) do not have to be cell-surface proteins, but can be intracellular or even intranuclear proteins. These molecules may represent ideal immunotherapeutic targets because they may be directly involved in the dysregulation of cell growth associated with cancer development.

Tumor-specific CTLs have been found with neuroblastomas, malignant melanomas, sarcomas, and carcinomas of the colon, breast, cervix, endometrium, ovary, testis, nasopharynx, and kidney. The significance of immune reactions in controlling tumor growth is not clear, but it seems likely that T cells can damage tumor cells in vivo under some conditions. Natural killer (NK) cells, which can kill tumor cells, are also found in persons without tumors. NK cells appear to recognize certain common features of tumor cells, particularly low levels of class I MHC molecules. Some T cells require the presence of humoral antibodies directed against the tumor cells (antibody-dependent cellular cytotoxicity) to initiate the interactions that lead to the death of tumor cells.