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The tumor microenvironment (TME) exerts key effects on tumor development, progression and treatment. Therefore, a quantitative understanding of various cellular and molecular interactions in the TME is very important. In this study, we combined a dynamic model and data analysis to quantitatively explore how microenvironmental factors influence tumor growth and three phases of cancer immunoediting. First, we presented a model system of partial differential equations (PDEs) using four main types of cells within the microenvironment of solid tumors and used two sets of published experimental data to validate the model. Accordingly, the partial rank correlation coefficient (PRCC) was calculated to identify the sensitive parameters related to significant biological processes. Furthermore, numerical simulations indicated that the power of tumor proliferation exerts a substantial effect on the state of malignancy, but tumor control is achieved by adjusting sensitive microenvironmental factors, such as immune intensity and the proliferation of cancer-associated fibroblasts (CAFs). Moreover, we used two indicators to quantify three states, i.e., elimination, equilibrium and escape from cancer immunoediting. The quantitative analysis of the TME revealed that immune cells and CAFs dynamically guide the transition of the three states of immunoediting, namely, how these related factors affect the capacity of the immune system to eliminate developing tumor cells, hold them in an equilibrium state, or facilitate their expanded growth. These quantitative results provide new insights into how various microenvironmental changes mediate both natural and therapeutically induced cancer immunoediting responses. [ABSTRACT FROM AUTHOR]

The immune system plays a dual role in cancer. It conveys protective immunity but also facilitates malignant progression, either by sculpting tumor immunogenicity or by creating a microenvironment that can stimulate tumor outgrowth or aid in a subsequent metastatic cascade. Innate lymphoid cells (ILCs) embody this functional heterogeneity, although the nature of their responses in cancer has only recently begun to be unveiled. We provide an overview of recent insights into the role of ILCs in cancer. We also discuss how ILCs fit into the conceptual framework of cancer immunoediting, which integrates the dual role of the immune system in carcinogenesis. A broader understanding of their relevance in cancer is essential towards the design of successful therapeutic strategies. Highlights ILCs have been implicated in both tumor-suppressing and tumor-promoting activities. The possibility to enhance and/or reorient their tumor-suppressing and/or tumor-promoting activities, respectively, provides an opportunity to design putative successful therapeutic approaches. Insights into how cancer cells regulate ILC function represent an important area of unfulfilled need towards the design of therapeutic strategies. An improved understanding of the biology of ILCs could help in the management of immunotherapy-related side effects arising from treatments, including those stemming from immune checkpoint blockade therapy. [ABSTRACT FROM AUTHOR]

While persistent infection with oncogenic types of human Papillomavirus (HPV) is required for cervical epithelial cell transformation and cervical carcinogenesis, HPV infection alone is not sufficient to induce tumorigenesis. Only a minor fraction of HPV infections produce high-grade lesions and cervical cancer, suggesting complex host–virus interactions. Based on its pronounced immunoinhibitory properties, human leukocyte antigen (HLA)-G has been proposed as a possible prognostic biomarker and therapeutic target relevant in a wide variety of cancers and viral infections, but to date remains underexplored in cervical cancer. Given the possible influence of HLA-G on the clinical course of HPV infection, cervical lesions and cancer progression, a better understanding of HLA-G involvement in cervical carcinogenesis might contribute to two aspects of fundamental importance: 1. Characterization of a novel diagnostic/prognostic biomarker to identify cervical cancer and to monitor disease stage, critical for patient screening; 2. Identification of HLA-G-driven immune mechanisms involved in lesion development and cancer progression, leading to the development of strategies for modulating HLA-G expression for treatment purposes. Thus, this systematic review explores the potential involvement of HLA-G protein expression and polymorphisms in cervical carcinogenesis. [ABSTRACT FROM AUTHOR]

Abstract: Tumorigenesis implies adaptation of tumor cells to an adverse environment. First, developing tumors must acquire nutrients to ensure their rapid growth. Second, they must escape the attack from the host immune system. Recent studies suggest that these phenomena could be related and that tumor cell metabolism may propel tumor immune escape. Tumor cell metabolism tends to avoid mitochondrial activity and oxidative phosphorylation (OXPHOS), and largely relies on glycolysis to produce energy. This specific metabolism helps tumor cells to avoid the immune attack from the host by blocking or avoiding the immune attack. By changing their metabolism, tumor cells produce or sequester a variety of amino acids, lipids and chemical compounds that directly alter immune function therefore promoting immune evasion. A second group of metabolism-related modification targets the major histocompatibility complex-I (MHC-I) and related molecules. Tumor MHC-I presents tumor-associated antigens (TAAs) to cytotoxic T-cells (CTLs) and hence, sensitizes cancer cells to the cytolytic actions of the anti-tumor adaptive immune response. Blocking tumor mitochondrial activity decreases expression of MHC-I molecules at the tumor cell surface. And peroxynitrite (PNT), produced by tumor-infiltrating myeloid cells, chemically modifies MHC-I avoiding TAA expression in the plasma membrane. These evidences on the role of tumor cell metabolism on tumor immune escape open the possibility of combining drugs designed to control tumor cell metabolism with new procedures of anti-tumor immunotherapy. This article is part of a Directed Issue entitled: Bioenergetic dysfunction, adaptation and therapy. [Copyright &y& Elsevier]

Abstract: The concept of cancer immunotherapy stems from the proposed function of the immune system, called immunosurveillance, to protect against growing tumors. Due to genetic aberrations, tumor cells display an altered repertoire of MHC-associated peptides that can lead to the activation of immune cells able to eliminate the transformed cells. In some instances, under the pressure of the immune system, both the tumor and its microenvironment are shaped and immune-resistant tumor variants are selected initiating the process of cancer immunoediting. This can impair not only host-generated immunosurveillance, but also attempts to harness the immune response for therapeutic purposes, namely immunotherapy. Rather than being an exhaustive review of the different approaches of cancer immunotherapy, the focus of this review is to provide the reader with future challenges of the field by proposing ‘second generation’ immunotherapy approaches that take into account immunosubversive mechanisms adopted by tumor cells. After an introduction on the process of immunosurveillance and immunoescape we will analyze why current immunotherapy approaches have not fulfilled their promise and will finish by summarizing what are the challenges for future approaches. [Copyright &y& Elsevier]

Interferon-gamma (IFNγ) is a cytokine that plays physiologically important roles in promoting innate and adaptive immune responses. The absence of IFNγ production or cellular responsiveness in humans and experimental animals significantly predisposes the host to microbial infection, a result that validates the physiologic importance of this cytokine in preventing infectious disease. Recently, an additional role for IFNγ in preventing development of primary and transplanted tumors has been identified. Although there now appears to be a consensus that IFNγ promotes host responses to tumors, the mechanisms by which this cytokine achieves its effects remain unclear. In this review, we briefly discuss key issues of the molecular cell biology of IFNγ and its receptor that are most relevant to IFNγ-dependent anti-tumor effects and then focus on the data implicating IFNγ as a critical immune system component that regulates tumor development. Potential mechanisms underlying IFNγ’s anti-tumor effects are discussed and a preliminary integrative model of IFNγ’s actions on tumors is proposed. Finally, the capacity of IFNγ and lymphocytes to not only provide protection against tumor development but also to sculpt the immunogenic phenotype of tumors that develop in an immunocompetent host is presented and introduced as a “cancer immunoediting” process. [ABSTRACT FROM AUTHOR]