The fact that tumors are composed of both tumor cells and host cells has long been known. These tumor-associated cells include vascular endothelial cells and pe- cytes, as well as inflammatory cells such as neutrophils, monocytes, macrophages, mast cells and eosinophils, and lymphocytes. The tumor cells also interact with stromal cells and with elements of the tissue extracellular matrix. What has been less appreciated is the role that these cells could have in modulating the growth, invasion, and metastasis of the tumor. Early on, the elements of what we now call the tumor microenvironment were considered to be more or less innocent bysta- ers to the role of the tumor cells as they grew and invaded local sites. Today, there is an increased understanding of the critical role of the tumor microenvironment as dramatically influencing the course of tumor development and dissemination. This volume represents a superb compilation of the latest thoughts and data regarding the role of each essential component of the tumor microenvironment in cancer development and progression. Perhaps, the earliest recognition of the role of nonmalignant cells as cancer re- lators was the recognition that lymphocytes can participate in what was termed “immune surveillance” in the 1960s. Our understanding of tumor immunity has improved markedly since then, and there are now successful clinical studies sh- ing the potential use of immune-based therapies in cancer treatment.

Traditionally, the interplay between cancer cells and host immunity has been studied systemically. Recent studies, however, indicate that the tumor microenvironment is unique in providing both supportive and inhibitory factors that determine the fate of the tumor and its host. This volume compiles reviews on innate and adaptive immune responses at the tumor microenvironment with emphasis on positive and negative outcomes that affect the progression of the disease.

Revealing essential roles of the tumor microenvironment in cancer progression, this book focuses on the role of hematopoietic components of the tumor microenvironment. Further, it teaches readers about the roles of distinct constituents of the tumor microenvironment and how they affect cancer development. Topics include eosinophils, NK cells, γδ T cells, regulatory T Cells, Langerhans cells, hematopoietic stem cells, Mast cells, B cells and Microglia, and more. Taken alongside its companion volumes, Tumor Microenvironment: Hematopoietic Cells – Part B updates us on what we know about various aspects of the tumor microenvironment as well as future directions. This book is essential reading for advanced cell biology and cancer biology students as well as researchers seeking an update on research in the tumor microenvironment.

This book addresses the biological processes relevant to the immune phenotypes of cancer and their significance for immune responsiveness, based on the premise that malignant cells manipulate their surroundings through an evolutionary process that is controlled by interactions with innate immune sensors as well as the adaptive recognition of self/non-self. Checkpoint inhibitor therapy is now an accepted new form of cancer treatment. Other immuno-oncology approaches, such as adoptive cell therapy and metabolic inhibitors, have also shown promising results for specific indications. Immune resistance is common, however, limiting the efficacy of immunotherapy in many common cancer types. The reasons for such resistance are diverse and peculiar to the immune landscapes of individual cancers, and to the treatment modality used. Accordingly, approaches to circumvent resistance need to take into account context-specific genetic, biological and environmental factors that may affect the cancer immune cycle, and which can best be understood by studying the target tissue and correlated systemic immune markers. Understanding the major requirements for the evolutionary process governing human cancer growth in the immune-competent host will guide effective therapeutic choices that are tailored to the biology of individual cancers.

Traditionally, the interplay between cancer cells and host immunity has been studied systemically. Recent studies, however, indicate that the tumor microenvironment is unique in providing both supportive and inhibitory factors that determine the fate of the tumor and its host. This volume compiles reviews on innate and adaptive immune responses at the tumor microenvironment with emphasis on positive and negative outcomes that affect the progression of the disease.

Tumor microenvironment (TME) plays an important role in immunosuppressive mechanisms that result in immune editing and treatment resistance. Elucidating the diversity of stromal and immune cell distribution, polarization, and changes in their gene expression signatures will enable a better understanding of key events to improve treatment and prognosis. With the onset of immune checkpoint inhibitors (ICIs) in clinics for patients with solid tumors and hematologic malignancies, immunotherapy has taken a new direction in cancer management, especially as combination therapies. However, limitations encountered with the use of ICIs, including toxicity and immune-related adverse events (irAE) indicate the need to understand multiple regulatory mechanisms at both cellular and molecular levels that alter the immune landscape of the TME. Since predominant changes in the immune landscape occur at the TME, focussed deliberation on these events will provide a comprehensive understanding on this topic for scientists in the fields of basic, translational, and clinical cancer immunology. The heterogeneity of TME and complex immune landscape pose major challenges in the treatment of solid tumors. Thus, integrative approaches, which relate immune mechanisms in the TME to that of peripheral and systemic immune signatures are essential to improve our understanding of the disease complexity and possibly improve immunotherapy outcomes. Such multiparametric studies should combine advances in current understanding of cancer immunobiology with powerful technologies, such as single-cell and spatial transcriptomics, and high dimensional flow cytometry that rapidly expand our ability to explore these interactions. Notably, tumor heterogeneity and inflammatory mediators in the TME vary significantly in neoplasms based on mutational load, lymphocyte infiltration, expression of checkpoint molecules, soluble inhibitors, and tumor cell metabolism. Overall, connecting key events to immune signatures that conform to a consensus will provide a benchmark to delve further into this important topic. Other parameters such as myeloid and lymphoid cell polarization to alter the immune homeostasis at the TME, favoring a tumor-supportive milieu would provide a macroscopic picture that may help guide treatment choices for more refined personalized tumor immunotherapy.

The tumor microenvironment has become a very important and hot topic in cancer research within the past few years. The tumor microenvironment is defined as the normal cells, molecules, and blood vessels that surround and feed a tumor cell. As many scientists have realized, studying the tumor microenvironment has become critical to moving the field forward, since there are many players in a tumor’s localized and surrounding area, which can significantly change cancer cell behavior. There is a dual relationship wherein the tumor can change its microenvironment and the microenvironment can affect how a tumor grows and spreads. Tumor Microenvironment in Cancer Progression and Cancer Therapy aims to shed light on the mechanisms, factors, and mediators that are involved in the cancer cell environment. Recent studies have demonstrated that in addition to promoting tumor progression and protecting tumor cells from the spontaneous immune-mediated rejection and different forms of cancer therapeutics, tumor microenvironment can also be a target and mediator of both standard and newly-emerging forms of cancer therapeutics. Thus, the dual role of the tumor microenvironment is the integral focus of the volume. The volume highlights the bi-directional interactions between tumor cells and non-malignant tumor component during tumor progression and treatment. It also focuses on the three groups of the reactive tumor component: stromal cells, blood vessels and the infiltrating immune cells. These three groups are discussed under the lens of their role in promoting tumor growth, shielding the tumor from rejection and from standard forms of cancer therapies. They are emerging as targets and mediators of standard and new forms of potential therapy.