Abstract:Wipe out bad seeds and plough in good soils: Immunotherapy flickers a new ray of hope in curing cancer

Abstract:Cancer pathogenesis in human is comprised by a series of complicated biological processes, whereby the rivalry between foreign tumor and inherent immunity determines the success or failure of this defense battle. As the “seed and soil” hypothesis implicated, tumor initiation and progression are not only driven by (epi) genetic abnormalities, but also influenced by surrounding tumor microenvironment, which adds another layer of understanding to cancer biology. More importantly, growing microenvironment-related studies provide the theoretical reasons for developing more effective cancer immunotherapy in clinical practice. In this review, we will present an overview of tumor microenvironmental components involving immune tolerance, as well as selective research advances in cancer immunotherapy.

Abstract:Cell metabolism has been widely studied in cancer development since Otto Warburg’s description of overwhelmed glycolysis in cancer cells in the 1920s. Accumulated evidence demonstrates that cancer cells upon hypoxia and nutrient stress could hijack and reprogram variously metabolic pathways, including anabolism and catabolism, to produce essential precursors for biomass synthesis to sustain cell survival and proliferation. In addition, metabolic alterations control cellular events at multiple levels such as transcription, epigenetics, translation and posttranslational modification, eventually play an essential role during cancer initiation and progression. Therefore, dysregulation of cancer metabolism has been generally recognized as one of the ten hallmarks of cancer. During last three decades, especially in the recent decade, studies on oncogenes, tumor suppressors, growth factor-associated signaling pathways, and cancer microenvironment, which sequentially take center stage of cancer biology research, reveal that the cancer metabolism is regulated by reciprocal interaction between cancer cells and surrounding microenvironment. Elucidating the function and mechanism of cancer microenvironment-mediated metabolism reprogramming will provide potential biomarkers and therapeutic targets and fundamentally improve diagnosis and prognosis of cancer patients.

Abstract:Cancer progression and metastasis are the result of reciprocal interaction between cancer cells and the surrounding stromal components. Tumor stroma features with activation of fibroblasts to cancer-associated fibroblasts (CAFs) and active remodeling of extracellular matrix (ECM) in most solid tumors. CAFs and ECM remodeling are not only characteristics of malignant tumors, but also actively promote tumor progression and metastasis through multiple mechanisms. Strategies targeting CAFs and ECM remodeling may provide novel and powerful approaches in cancer therapeutics.

Abstract:Integrins are important components of tumor microenvironment, which act as adhesion molecules located on cell surface. Integrins can recognize and interact with different ligands in order to participate in many important physiological processes, including tumor cell invasion and metastasis. Integrin activation mediates tumor cell metastasis, and reversely tumor microenvironment can influence the expression and activation of integrin, and thus promotes tumor progression.

Abstract:Human viral oncogenesis is a complex process with the multistep nature of oncogenesis. Tumor micro-environmental factors including immune cells and cytokines contribute to the biology of multistep oncogenesis mediated by established human oncoviruses. Interaction between oncoproteins and tumor microenvironment (TME) usually leads to immune suppression, thereby promoting cancer development. In this review, current status and perspectives of the research field in the impact of oncoviral proteins on TME are discussed, including Epstein-Barr virus (EBV), high-risk human papilloma viruses (HPVs), and hepatitis B virus (HBV) respectively.

Abstract:The success of cancer immunotherapy demonstrates the critical involvement of host immune system on cancer cell killing as well as the feasibility of anti-tumor immunity, whereas the immunosuppressive tumor microenvironment restrains the step forward of cancer immunotherapy. Tumor microenvironment is able to induce tumor metabolic reprogramming and this process leads to: (1) competitive utilization of nutrients between tumor cell and host immune cells; (2) regulation of activation and effector function of immune cells caused by tumor derived metabolites or waste through different modes. Thus, this review focuses on current views of the influence of tumor metabolic reprogramming and relevant metabolites on host immune, in order to provide theoretical basis and new ideas for cancer immunotherapy.

Abstract:Cancer stem cells (CSCs) maintain tumor propagation and heterogeneity due to their capacities of self-renewal and plasticity. Given that the CSCs are responsible for tumor formation, metastasis, drug resistance and relapse, the hypothesis of CSCs has been gradually accepted by more and more tumor researchers. Therefore, it is of great scientific and clinical significance to investigate CSC biology. The CSCs reside in niches (CSC niches), which are part of tumor microenvironments, containing cell-cell contact and secretory factors. Cancer non-stem cells and CSCs themselves also serve as the CSC niches. CSC niches maintain the plasticity of CSCs, protect CSCs from attack by the immune system, and promote tumor metastasis as well. The remodeling of CSC niches by CSCs, the influence of CSC self-renewal by CSC niches, and CSC niche-based targeted interventions emerge as fronts of CSC biology. In this review, we summarize recent progresses on CSC discovery, CSC self-renewal regulation, CSC niches, as well as targeted interventions against CSCs and CSC niches.

Abstract:Tumor immunotherapy has now become a new effective therapy against cancer, as a way to use the patient’s own immune system to achieve anti-tumor effect. However, the presence of inhibitory tumor microenvironment can greatly reduce the effect of immunotherapy. Base on the tumor microenvironment composition, classification and the effect of treatment, we explore ways to deal with the inhibition of tumor microenvironment through radiotherapy, chemotherapy, checkpoints, gene modified immune cells and combination therapy, to make the greatest effect of immunotherapy.