What exactly is cancer? Cancer is a disease that begins when a normal cell undergoes a sequence of genetic and epigenetic alterations. Cancer is a disease of the microenvironment and immunity, in addition to the malignant cell itself. Although genetic and epigenetic changes drive cellular transformation, genomic plasticity, and evolvement, it has become clear that multiple signals delivered within the tumor microenvironment by modifier genes, stromal and endothelial cells, and immune cells are critical factors in determining whether an initiated lesion progresses versus dormancy or destruction, as well as whether or not metastasis occurs.
How did this schism occur? In this section, we examine how these workers were divided in the past and discuss why it is now vital to promote increased cross-fertilization. We emphasize three themes in particular that we feel are crucial for discussion and debate. The first concept is that treatment techniques that fail to harness the immune system frequently are overcome by tumor resistance, owing to the wide “genomic space” that genetically plastic tumor cells may easily access to create resistance mechanisms. Because all medicines promote tumor development by imposing a selection for resistant cells, leveraging the flexibility of the immune system will be critical to finally halting the tumor cell’s lethal adaptability.
We propose that the mechanisms that promote the formation of a “smoldering” inflammatory milieu in cancer coincide with those that promote tumoral immune escape. If this is accurate, removing immune suppression will shift the tumor’s inflammatory state from supportive to destructive. The third hypothesis is that, by removing immunosuppressive processes, cytotoxic chemotherapy may complement, rather than compete with, active immunotherapy. Provocative preclinical research in this area has sparked a clinical interest. We think that increasing efforts to integrate cancer immunologists’ viewpoints and work with cancer biologists and pharmacologists will be required to meet the National Cancer Institute’s aim of controlling cancer in the clinic by 2015.
Senior Immunologist Dr. Paul E Love and his substantial Research
Dr. Paul Ernest Love is a clinical pathologist and immunologist from the United States. Dr. Love has over 31 years of experience as a Scientist and is credited with significant research achievements in fundamental science and medicine. Dr. Love works at the National Institutes of Health (NIH), a government institution that is part of the US Department of Health and Human Services. He is still a key player at the NIH and is well-known in the field of immunology. Dr. Love now serves as the Section Head of Hematopoiesis and Lymphocyte Biology at the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). His studies largely focus on T cell antigen receptor (TCR) signaling, with a specific emphasis on the involvement of immuno-receptor-tyrosine based receptors.
Dr. Love was born on April 15, 1957, to father Lyman M. Love and Mother Janet E. Love (née Wagner) (nee Wagner). Dr. Love graduated from Syracuse University in 1979 with a B.S. in Biochemistry, Summa Cum Laude, and was chosen to the Phi Beta Kappa honor organization. Dr. Love earned his M.D. and Ph.D. in 1987 from the University Of Rochester School Of Medicine. He finished a residency program in Laboratory Medicine at Washington University in St. Louis, where he authored a seminal study of antiphospholipid antibodies in SLE. After completing his residency, he went on to complete a fellowship in Medical Genetics at the NICHD before undertaking post-doctoral research at the NIH.
Love developed one of the first gene-targeted models at NIH as a postdoctoral fellow, mice missing expression of the CD3zeta chain of the T Cell Antigen Receptor (TCR). As a result, his lab has created mice defective in multiple different TCR subunits. Understanding the nature and function of the TCR’s numerous signal-transducing modules known as Immuno-receptor-Tyrosine-based-Activation-Motifs (ITAMs) has been a long-term focus of research at the Love-laboratory. T cells, one of the lymphocyte types required to combat infectious diseases, utilize ITAMs. T cells also identify and eliminate cancer cells and play an important part in self/non-self-identification.
Dr. Love’s lab is looking at whether changing the TCR ITAM sequences will increase T cell activation and function, particularly tumor cell killing capacity. As a result, this research is looking at whether TCR signal transducing subunits may be ‘tuned’ to improve TCR-mediated cell activation and tumor killing. The second line of study focuses on developing and characterizing a family of molecules called tuning molecules, which operate as a signal regulating proteins to attenuate TCR signals. Though discovered in mice, tuning molecules are also found in human T cells, making them appealing therapeutic targets.