Cancer immunology: highlights of the NCI Extramural Immunology Program

The long-term goal of research supported by the Immunology Program is to better understand immune mechanisms and their regulation in order to develop more effective strategies to strengthen the immune response against cancer. While there has been much progress in the field of immunology in recent years, many major questions remain unanswered. The role of MHC antigens in regulating the immune response to tumors is still unclear, as is the nature of putative tumor-associated antigens which are the targets of this response. The efficacy of various immune cell subsets in tumor cell killing is differentially affected by changes in tumor cell surface MHC antigen expression. Furthermore, although we now know much more about the cellular interactions in the immune response, little is actually known about the particular cell subsets which participate in an immune response is regressing versus progressing tumors. Interleukins have been shown to stimulate a variety of immunes response, and some of these immune modulators are now being tested in clinical trials, in various stages, to determine their antitumor effects. However, systemic administration of large quantities of interleukins can result in very different effects than those created by the local release of effector molecules from specific T-cell populations. Effector T cells can deliver lymphokines to precise target structures, whereas systemically administered lymphokines would affect preferentially those cells expressing the largest numbers of high affinity receptors for the lymphokines. The specificity of lymphokines as mediators of immunologic response rests largely or exclusively in the local release of such materials by T cells upon activation by antigen: MHC complexes on a stimulating cell. Because lymphokines show specificity only for nonantigen-specific, non-MHC-restricted receptor molecules on target cells, the effect of lymphokine injections is likely to be determined solely by the expression of these receptors. Thus, lymphokines function well as effector molecules in a number of specific immune reactions, but it remains to be determined whether they will be useful in regulating immune responses in specific disease situations. It may be critical to recruit specific immune cells to the area of tumor growth where they, in turn, can release lymphokines to activate appropriate antitumor effector cells. Adoptively transferred T cells of the helper phenotype can induce an effective antitumor immune response in recipient mice.(ABSTRACT TRUNCATED AT 400 WORDS)