Keystone Symposia: Molecular and Cellular Biology of Immune Escape in Cancer (J6)

It is now widely recognized that the immune microenvironment of a tumor provides critical support in determining its progression versus dormancy or destruction. To gain immune benefits the tumor must evolve mechanisms of immune escape. Study of this crucial process requires cross-fertilization between molecular cell biologists and tumor immunologists who do not tend to interact. This problem is also integrated with the problem of cancer inflammation that has captured the attention of tumor biologists focused on transgenic mouse models and clinical settings. Thus, we propose a unique conference the first of its kind to integrate perspectives from a diverse set of researchers in cancer, immunology, and molecular therapeutics and to focus specifically on immune escape and tumor-induced immune suppression as a multidisciplinary problem. Cancer is initiated by the accumulation of genetic and epigenetic changes in a normal cell, but its progression depends on the stromal and immune microenvironment of the initiated cell. While intrinsic signals within the initiated cell drive neoplastic transformation and genomic plasticity, extrinsic signals delivered by immune cells are critical in dictating whether progression versus dormancy or destruction of an initiated lesion takes place, and also whether metastasis may occur. The high degree of genomic plasticity in cancer cells permits them to develop sophisticated ways to prevent the immune system from recognizing and eliminating tumor cells. It has become increasingly clear in recent years that abnormalities in the immune system that are induced by tumors not only hamper natural anti-tumor immune surveillance but also limit the efficacy of immunotherapy and even traditional chemotherapy and radiotherapy. Thus, tumor-induced immune abnormalities may not only impact the clinical course of disease but also the prospects for its therapeutic management. Recent results indicate that we are on the verge of a real breakthrough in our understanding of how tumors thwart the immune system and how correcting immune escape could vastly improve cancer therapy. However, at present the available mechanistic information presents a somewhat convoluted picture that includes some seemingly contradictory elements. While this situation is a natural stage of development in the field, there is nevertheless a pressing need to define key questions and organize their development in coherent ways that can speed improvements in cancer therapy.