Over the past decade, the tumor microenvironment has become one of the most important research areas in cancer biology, as cells within the tumor microenvironment, despite being outnumbered by healthy cells, are able to evade surveillance and immune-mediated destruction. While researchers have learned a great deal about the cellular and structural makeup of the tumor microenvironment, there has been a growing understanding of the metabolic interplay between the tumor micronenvironment’s various cellular constituents and how each of them contributes to overall tumor growth and metastases. This new volume will guide researchers, students, oncologists and academics through a rapidly developing and changing field with a thorough understanding of tumor microenvironment biology from a cellular, structural, metabolic, and immunological perspective.

Genetic alterations in cancer, in addition to being the fundamental drivers of tumorigenesis, can give rise to a variety of metabolic adaptations that allow cancer cells to survive and proliferate in diverse tumor microenvironments. This metabolic flexibility is different from normal cellular metabolic processes and leads to heterogeneity in cancer metabolism within the same cancer type or even within the same tumor. In this book, we delve into the complexity and diversity of cancer metabolism, and highlight how understanding the heterogeneity of cancer metabolism is fundamental to the development of effective metabolism-based therapeutic strategies. Deciphering how cancer cells utilize various nutrient resources will enable clinicians and researchers to pair specific chemotherapeutic agents with patients who are most likely to respond with positive outcomes, allowing for more cost-effective and personalized cancer therapeutic strategies.

Metabolism of glucose, lipids, amino acids, and nucleotides represents the fundamental capability of host to utilize distinct nutrients and energy to support diverse function of different cell lineages. Cancer cells undergo the Warburg Effect to adapt to the microenvironment composed by stromal cells and immune cells. The crosstalk among cancer cells and immune cells orchestrate tumor progression. In the tumor microenvironment, immune cells also show metabolic reprogramming. For example, naive or memory T cells switch from the oxidation of fatty acids to glycolysis and glutaminolysis after activation; meanwhile massive glucose and glutamine are transported into cells to meet their metabolic demands. Defective glucose or glutamine metabolism impairs the differentiation and expansion of helper T cells. The molecular pathways that control immune cell metabolism and function are intimately linked. Understanding such metabolic reprogramming of immune cells in the tumor microenvironment could offer new directions in manipulation of peripheral immune responses. Recent findings in immune cell metabolism hold the promising possibilities by metabolic manipulation of immune cells towards clinical therapeutics for treating cancer. This Research Topic includes updated findings and views in the metabolism of cancer cells and immune cells in the tumor microenvironment.

This book focuses on lipid metabolism in tumor immunity, covering the application of lipidomics in tumor immunity and all aspects of lipid metabolism in tumor microenvironment. During the progression of tumors, tumor cells and immune cells interact in a dynamic microenvironment. Targeting the immune system has a high potential for treating cancer. However, due to the high heterogeneity of the tumor microenvironment, only a small percentage of patients experience such clinical benefits of tumor immunotherapy. Therefore, understanding the tumor microenvironment is crucial for tumor immunity. Recently, lipid metabolism is an emerging research direction and contributes to cell survival and biofunctions in tumor microenvironment, which is of great interest and significance to be elucidated. This book provides the doctors, researchers, and scientists with a cutting-edge overview of the lipid metabolism and its role in tumor immunity. It also yields benefits for pharmaceutical companies regarding drug discovery.

The collection of chapters in this proceeding volume reflects the latest research presented at the Aegean meeting on Tumor Microenvironment and Cellular Stress held in Crete in Fall of 2012. The book provides critical insight to how the tumor microenvironment affects tumor metabolism, cell stemness, cell viability, genomic instability and more. Additional topics include identifying common pathways that are potential candidates for therapeutic intervention, which will stimulate collaboration between groups that are more focused on elucidation of biochemical aspects of stress biology and groups that study the pathophysiological aspects of stress pathways or engaged in drug discovery.

The way a cell undergoes malignant transformation should meet their capacity of surviving in the microenvironment of the organ where the cancer will develop. Metabolic adaptation is for sure one of the criteria that must be accomplished, driven by metabolic plasticity that allows the adaptation of cancer cells to the availability of energy and biomass sources that will sustain cell survival and proliferation. Each human organ has a particular microenvironment which depends on several cell types and in some cases also on symbiotic microorganisms. These biological partners are constantly sharing organic compounds and signaling molecules that will control mitogenesis, cell death and differentiation, accounting for the organ's function. Nevertheless, cancer cells are capable of taking advantage of this metabolic and signaling microenvironmental dynamics. In this book, we intend to present the different components of the microenvironment driving the metabolic fitness of cancer cells. The metabolic changes required for establishing a tumor in a given microenvironment and how these metabolic changes limit the response to drugs will generally be the major items addressed. It is important to mention not only aspects of the microenvironment that stimulate metabolic changes and that select better adapted tumor cells, but also how this regulation of cell plasticity is made. Thus, the signaling pathways that orchestrate and are orchestrated throughout this panoply of metabolic rearrangements will also be addressed in this book. The subjects will be presented from the conceptual point of view of the cross-cancer mechanisms and also particularizing some models that can be examples and enlightening within the different areas.

This book discusses the novel metabolic cross-talk between immune and tumor cells in the tumor microenvironment that promotes their growth and progression. It also describes deregulated metabolism in cancer cells that promotes suppressive and cancer cell-favourable microenvironment. Further, the book provides novel insights on the metabolic changes in immune cells that promote tumor cell growth and survival. In turn, it also reviews the involvement of immuno-onco metabolic cross-talk in the development of resistance to chemo-radiation therapy (CRT) in tumor cells. Lastly, it also explores the potential of immuno-oncology metabolism as a therapeutic approach against tumor cells.