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Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland
1Correspondence: Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland 20892. E-mail: hrosenberg{at}niaid.nih.gov
HOW DID THIS SPECIFIC PROJECT GET STARTED?
This project had a particularly interesting beginning. For many years, Jamie wondered about the strange notation system used in the laboratory. In fact, the initial entries relating to the project featured in Pivotal Advance "Eosinophil infiltration of solid tumors is an early and persistent inflammatory host response" could be traced to a ten-year-old notebook, under the heading DTJ 23.2. DTJ? Detailed Text Journal? Defined Tumor J... . ? Well, not exactly. These were apparently the projects which everyone in the group understood to be designated "Don’t Tell Jamie" ... or at least Don’t Tell Jamie until it was clear exactly how these projects were to be funded. In the Lee laboratories, Jamie credits Nancy with the foresight to push forward with new concepts and directions, while he keeps tabs on the bottom line. It is clearly a formula that works. The Lees have made many prominent contributions to leukocyte biology, and they have made particular strides toward elucidating the role of the eosinophil in allergic lung dysfunction and asthma. Among Nancy and Jamie Lee’s many accomplishments are several published manuscripts which define a causative role for eosinophils in mouse models of allergen-induced asthma [1 , 2 ]. In their recent paper appearing in Science [3 ], the Lees describe the development of a transgenic suicide-inactivation strategy that yielded an eosinophil-free mouse, which elucidated a role for eosinophils in goblet cell metaplasia/epithelial mucin accumulation and lung dysfunction such as allergen-induced airway hyperresponsiveness. Equally intriguing is their recent review [4 ] in which they consider the historical literature on eosinophils and present an alternative view of the evolution and function of this enigmatic leukocyte.
The study featured in this Pivotal Advance takes on a historically significant and important subject: the role of the eosinophil in the inflammatory response to human tumors. As noted in the introduction to the manuscript, the earliest histological reports of solid tumors include descriptions of eosinophils. Yet, to this day, there is no consensus as to whether tissue eosinophilia is a favorable or unfavorable prognostic indicator.
IS THE STUDY OF EOSINOPHILS AND SOLID TUMORS A COMPLETELY NEW DIRECTION FOR THE LABORATORY?
The study of the role of eosinophils in solid tumors represents a new direction for the laboratory, but it is the rejuvenation of an old research interest for Nancy Lee. As an undergraduate at the University of Memphis, Nancy studied organic chemistry, and spent significant time on a project involving slow neutrons’ interactions with boron nuclei, with the ultimate goal of local generation of gamma irradiation for therapeutic purposes. She has always held an interest in nontraditional chemotherapeutic agents for targeting tumors, and this new finding regarding eosinophils will be directed toward this experimental end.
WHAT IS THE SPECIFIC ROLE OF EOSINOPHILS IN RELATION TO SOLID TUMORS?
From the perspective of cancer biology, the study of eosinophils and solid tumors has both old and new aspects. Eosinophils can have multiple proinflammatory functions in this setting, both positive and negative, as they may elicit angiogenesis as well as promote scavenging and remodeling. Previous mouse model studies using cytokine-expressing malignant cells have provided some perspective on the functions of eosinophils against tumor targets. However, the studies performed by the Lee laboratories utilize an unmanipulated tumor in wild-type mice, and as such, permit eosinophil function to be studied in a more natural setting. At present, the Lees have found somewhat limited perspective and interest in this line of work on the part of the mainstream cancer research community, a point of view that they believe will ultimately change as more data emerge.
HOW WILL THE WORK PROGRESS FROM HERE?
Among the interesting directions to follow from this Pivotal Advance, the Lees intend to explore links between eosinophil activity and primary tumor growth and kinetics of metastasis. Once these links have been established, identification of the role of unique eosinophil-specific granule proteins would certainly be a significant advance toward understanding the molecular aspects of eosinophil-mediated functions. Information obtained from experimental data could then be applied to patient therapy, particularly the targeting of eosinophils to solid tumors as a form of directed inflammatory therapy.
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