What's new in the local immune response in cancer?

Malignant tumors in humans are commonly associated with an inflammatory infiltrate. The mechanisms that account for the accumulation of T-lymphocytes and macrophages--these cells comprise the major components of tumor infiltrates--in the vicinity of a growing tumor are not fully understood. Tumor specific and immunogenic antigens could not be demonstrated in most solid tumors of humans, in contrast to several experimental tumor models. Thus it is not proven in human malignancies that neoantigens expressed on malignant cells are the signal which initiates an inflammatory response that, immunohistologically, is comparable to mononuclear infiltrates present in allograft rejection. A variety of nonspecific factors including lymphokines released by tumor cells may also account for the accumulation of inflammatory cells at the tumor site. The difficulties to evaluate the functional role of the "local immune response" for tumor and host are even greater. Most tumors progress in the presence of mononuclear infiltrates. Do they progress in spite of or because of the action of the local immune response? Clinical, immunopathological, and experimental data suggest that both is right, and that at least four distinct properties of tumor-associated immune reactions exist: Regression, Selection, Modulation and Progression. These distinct properties will be discussed below, using mainly the malignant melanoma of the skin as a model for a malignant tumor in humans.