IMMUNOPHENOTYPE OF SOLID TUMORS AND TUMOR METABOLIC REPROGRAMMING

Abstract

ABSTRACTWith the technological advances in biotechnology that have been made high-throughput measurement of nucleic acids feasible and affordable, the tumor microenvironment (TME) has been intensively studied. Advances in therapy have made pharmacologic treatment of cancer more effective than ever before. However, in consideration of the expense of the new class of monoclonal immunotherapeutic antibodies, their occasionally serious side effect profile, and a somewhat limited spectrum of activity among patient cohorts, there has come a great demand to understand the factors which make individual cases of cancer differ. Many approaches to address the issue of individual patient response to immunomodulatory antibodies have been devised. Both traditional, bench-based approaches and more modern, bioinformatical solutions have yielded important insights into the problem. Unfortunately, many difficult and important questions have remained unexplained. In particular, a general theory that is capable of explaining the broadest similarity of observed clinical responses to therapy with monoclonal immunotherapeutic agents across dissimilar patient cohorts that identifies a clear relationship to cellular and molecular features has been elusive. Understanding the most important concepts involved in tumor immunology requires drawing together some intermediate and detailed knowledge from several subdisciplines in biology and clinical medicine. In the studies presented here, elements of bioinformatic data analysis, details of immunological function, and knowledge of cellular and molecular processes relevant to cancer are reviewed in terms of published literature as an introduction. In a second segment, these topics of perceived relevance to studies of cancer are then highlighted with presentations of new findings based upon a novel bioinformatic approach. A summary is presented in Chapter 3 containing a brief discussion of how these findings impact the field with reference to current knowledge and practice, while a series of Appendices further substantiate the importance of these findings with brief details of a variety of related results.