Cellular immunotherapy and cancer

Recent data indicate that cellular immune responses can produce an anticancer effect. Two types of cellular immune responses appear to be clinically relevant: antigen specific immunity mediated by T cells that recognize tumor-associated peptide antigen expressed on surface HLA class I or class II molecules, and antigen nonspecific immune responses mediated by natural killer (NK) cells that are activated by the failure to recognize cognate "self" HLA class I molecules. The graft-versus-tumor effect of allogeneic transplants using HLA-matched donors is mediated by antigen-specific T cells, while allogeneic transplantation using HLA mismatched donors can also lead to donor NK cells with potent antitumor activity. HLA mismatched haplo-identical transplants can exert a powerful antileukemia effect based on expansion of antigen nonspecific donor NK cells, but slow recovery of donor T cells is associated with a profound immune deficiency and increased opportunistic infections that limit the overall clinical success of this type of transplant maneuver. The focus for most immunologic maneuvers designed to enhance the graft-versus-tumor effect has been on strategies to expand or enhance the activity of antigen-specific donor T cells that recognize host tumor cells. In the case of hematologic malignancies, the activity of donor T cells against tumor cells is regulated by dendritic cells, which can augment or inhibit cellular immune responses. Future successes in enhancing the patients' own cellular immune responses to cancer will likely be based on activation of T cells by the appropriate dendritic cell subset and, in the case of tumors that have down-regulated HLA class I expression, by activated NK cells.