scholarly journals Targeting ubiquitin signaling for cancer immunotherapy

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Xiaofei Zhou ◽  
Shao-Cong Sun
Keyword(s):  
Cancer Immunotherapy ◽  
Immune Cells ◽  
Protein Modification ◽  
Antitumor Immunity ◽  
Checkpoint Inhibitors ◽  
Therapeutic Approaches ◽  
Protein Ubiquitination ◽  
Advanced Malignancies ◽  
Novel Targets ◽  
Made In

AbstractCancer immunotherapy has become an attractive approach of cancer treatment with tremendous success in treating various advanced malignancies. The development and clinical application of immune checkpoint inhibitors represent one of the most extraordinary accomplishments in cancer immunotherapy. In addition, considerable progress is being made in understanding the mechanism of antitumor immunity and characterizing novel targets for developing additional therapeutic approaches. One active area of investigation is protein ubiquitination, a post-translational mechanism of protein modification that regulates the function of diverse immune cells in antitumor immunity. Accumulating studies suggest that E3 ubiquitin ligases and deubiquitinases form a family of potential targets to be exploited for enhancing antitumor immunity in cancer immunotherapy.

Nanoimmunotherapy – cloaked defenders to breach the cancer fortress

2018 ◽  
Vol 7 (4) ◽  
pp. 317-340 ◽  
Author(s):  
Gayathri Kandasamy ◽  
Vadim Annenkov ◽  
Uma Maheswari Krishnan
Keyword(s):  
Cancer Cells ◽  
Immune Cells ◽  
Immune Surveillance ◽  
Cancer Recurrence ◽  
Host Immune System ◽  
Therapeutic Approaches ◽  
Cytotoxic Effects ◽  
Cytotoxic Factor ◽  
Causes Of Mortality ◽  
Made In

AbstractCancer continues to be ranked among the top causes of mortality in the world despite the advances made in science and technology. The sub-par performance of cancer therapeutic strategies is due to the transformation of the cancer from a proliferating mass of cells into an impregnable fortress that manipulates and controls the microenvironment to prevent access to any potential cytotoxic factor as well as circumvent the innate immune surveillance processes. Recruitment of the native immune cells to selectively recognize and kill cancer cells can serve to augment the cytotoxic effects of conventional cancer therapeutic approaches. In addition to annihilation of the cancer cells, the induction of memory in the immune cells prevents the possibility of cancer recurrence. However, despite the apparent benefits of cancer immunotherapy, there are several pitfalls that need to be addressed in order to extend these benefits to the clinic. In this context, engineered nanostructured carrier systems can be effectively employed for an activation and priming of the host immune system selectively against the target cancer cells. This has led to the emergence of “nanoimmunotherapy” as an important therapeutic approach against cancer. The use of multi-functional nanomaterials in combination with immunotherapy offers possible solutions to overcome the current limitations in cancer therapy and represents the next generation of “smart therapeutics,” which forms the prime focus of discussion in this review.

scholarly journals Targeting hypoxia in the tumor microenvironment: a potential strategy to improve cancer immunotherapy

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Bin Wang ◽  
Qin Zhao ◽  
Yuyu Zhang ◽  
Zijing Liu ◽  
Zhuangzhuang Zheng ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Cancer Immunotherapy ◽  
Immune Suppression ◽  
Cell Biology ◽  
Immune Cell ◽  
Checkpoint Inhibitors ◽  
Intrinsic Property ◽  
Patients With Cancer ◽  
Potential Strategy ◽  
Made In

AbstractWith the success of immune checkpoint inhibitors (ICIs), significant progress has been made in the field of cancer immunotherapy. Despite the long-lasting outcomes in responders, the majority of patients with cancer still do not benefit from this revolutionary therapy. Increasing evidence suggests that one of the major barriers limiting the efficacy of immunotherapy seems to coalesce with the hypoxic tumor microenvironment (TME), which is an intrinsic property of all solid tumors. In addition to its impact on shaping tumor invasion and metastasis, the hypoxic TME plays an essential role in inducing immune suppression and resistance though fostering diverse changes in stromal cell biology. Therefore, targeting hypoxia may provide a means to enhance the efficacy of immunotherapy. In this review, the potential impact of hypoxia within the TME, in terms of key immune cell populations, and the contribution to immune suppression are discussed. In addition, we outline how hypoxia can be manipulated to tailor the immune response and provide a promising combinational therapeutic strategy to improve immunotherapy.

scholarly journals Cancer cell metabolic reprogramming: a keystone for the response to immunotherapy

2020 ◽  
Vol 11 (11) ◽  
Author(s):  
Michaël Cerezo ◽  
Stéphane Rocchi
Keyword(s):  
Tumor Microenvironment ◽  
Immune Cells ◽  
Metabolic Pathways ◽  
Immune Checkpoint Inhibitors ◽  
Antitumor Immunity ◽  
Checkpoint Inhibitors ◽  
Metabolic Reprogramming ◽  
Limited Resources ◽  
Antitumor Response ◽  
Secondary Resistance

Abstract By targeting the tumor microenvironment to stimulate antitumor immunity, immunotherapies have revolutionized cancer treatment. However, many patients do not respond initially or develop secondary resistance. Based on the limited resources in the tumor microenvironment and competition between tumor and immune cells, the field of immune metabolism has produced extensive knowledge showing that targeting metabolism could help to modulate antitumor immunity. However, among all the different potentially targetable metabolic pathways, it remains unclear which have more potential to overcome resistance to immune checkpoint inhibitors. Here, we explore metabolic reprogramming in cancer cells, which might inhibit antitumor immunity, and strategies that can be used to favor the antitumor response.

scholarly journals Harnessing tumor-associated macrophages as aids for cancer immunotherapy

2019 ◽  
Vol 18 (1) ◽  
Author(s):  
Xiaolei Li ◽  
Rui Liu ◽  
Xiao Su ◽  
Yongsha Pan ◽  
Xiaofeng Han ◽  
...  
Keyword(s):  
Solid Tumors ◽  
Immune Cells ◽  
Antitumor Immunity ◽  
Therapeutic Strategies ◽  
Therapeutic Approaches ◽  
Tumor Associated Macrophages ◽  
Therapeutic Modalities ◽  
Preclinical And Clinical Studies ◽  
Tumor Types ◽  
Cancer Immunotherapies

AbstractCancer immunotherapies that engage immune cells to fight against tumors are proving to be powerful weapons in combating cancer and are becoming increasingly utilized in the clinics. However, for the majority of patients with solid tumors, little or no progress has been seen, presumably due to lack of adequate approaches that can reprogram the local immunosuppressive tumor milieu and thus reinvigorate antitumor immunity. Tumor-associated macrophages (TAMs), which abundantly infiltrate most solid tumors, could contribute to tumor progression by stimulating proliferation, angiogenesis, metastasis, and by providing a barrier against antitumor immunity. Initial TAMs-targeting strategies have shown efficacy across therapeutic modalities and tumor types in both preclinical and clinical studies. TAMs-targeted therapeutic approaches can be roughly divided into those that deplete TAMs and those that modulate TAMs activities. We here reviewed the mechanisms by which macrophages become immunosuppressive and compromise antitumor immunity. TAMs-focused therapeutic strategies are also summarized.

scholarly journals Cancer Vaccines: Toward the Next Breakthrough in Cancer Immunotherapy

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Yuka Igarashi ◽  
Tetsuro Sasada
Keyword(s):  
Cancer Immunotherapy ◽  
Immune Cells ◽  
Immune Checkpoint ◽  
Cancer Vaccines ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Critical Role ◽  
Current Status ◽  
Problems And Solutions ◽  
Cancer Immunotherapies

Until now, three types of well-recognized cancer treatments have been developed, i.e., surgery, chemotherapy, and radiotherapy; these either remove or directly attack the cancer cells. These treatments can cure cancer at earlier stages but are frequently ineffective for treating cancer in the advanced or recurrent stages. Basic and clinical research on the tumor microenvironment, which consists of cancerous, stromal, and immune cells, demonstrates the critical role of antitumor immunity in cancer development and progression. Cancer immunotherapies have been proposed as the fourth cancer treatment. In particular, clinical application of immune checkpoint inhibitors, such as anti-CTLA-4 and anti-PD-1/PD-L1 antibodies, in various cancer types represents a major breakthrough in cancer therapy. Nevertheless, accumulating data regarding immune checkpoint inhibitors demonstrate that these are not always effective but are instead only effective in limited cancer populations. Indeed, several issues remain to be solved to improve their clinical efficacy; these include low cancer cell antigenicity and poor infiltration and/or accumulation of immune cells in the cancer microenvironment. Therefore, to accelerate the further development of cancer immunotherapies, more studies are necessary. In this review, we will summarize the current status of cancer immunotherapies, especially cancer vaccines, and discuss the potential problems and solutions for the next breakthrough in cancer immunotherapy.

scholarly journals Recent Progress in Dendritic Cell-Based Cancer Immunotherapy

Cancers ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2495
Author(s):  
Kazuhiko Matsuo ◽  
Osamu Yoshie ◽  
Kosuke Kitahata ◽  
Momo Kamei ◽  
Yuta Hara ◽  
...  
Keyword(s):  
Cancer Immunotherapy ◽  
Immune Checkpoint ◽  
Targeted Delivery ◽  
Cancer Vaccines ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Host Immune Responses ◽  
Near Future ◽  
Identification And Characterization

Cancer immunotherapy aims to treat cancer by enhancing cancer-specific host immune responses. Recently, cancer immunotherapy has been attracting much attention because of the successful clinical application of immune checkpoint inhibitors targeting the CTLA-4 and PD-1/PD-L1 pathways. However, although highly effective in some patients, immune checkpoint inhibitors are beneficial only in a limited fraction of patients, possibly because of the lack of enough cancer-specific immune cells, especially CD8+ cytotoxic T-lymphocytes (CTLs), in the host. On the other hand, studies on cancer vaccines, especially DC-based ones, have made significant progress in recent years. In particular, the identification and characterization of cross-presenting DCs have greatly advanced the strategy for the development of effective DC-based vaccines. In this review, we first summarize the surface markers and functional properties of the five major DC subsets. We then describe new approaches to induce antigen-specific CTLs by targeted delivery of antigens to cross-presenting DCs. In this context, the chemokine receptor XCR1 and its ligand XCL1, being selectively expressed by cross-presenting DCs and mainly produced by activated CD8+ T cells, respectively, provide highly promising molecular tools for this purpose. In the near future, CTL-inducing DC-based cancer vaccines may provide a new breakthrough in cancer immunotherapy alone or in combination with immune checkpoint inhibitors.

scholarly journals Cancer immunotherapy in special challenging populations: recommendations of the Advisory Committee of Spanish Melanoma Group (GEM)

2021 ◽  
Vol 9 (3) ◽  
pp. e001664
Author(s):  
Maria Gonzalez-Cao ◽  
Teresa Puertolas ◽  
Mar Riveiro ◽  
Eva Muñoz-Couselo ◽  
Carolina Ortiz ◽  
...  
Keyword(s):  
Cancer Immunotherapy ◽  
Multidisciplinary Approach ◽  
Checkpoint Inhibitors ◽  
Solid Organ Transplantation ◽  
Latent Tuberculosis ◽  
Solid Organ ◽  
Chronic Infections ◽  
Immunosuppressed Patients ◽  
History Of ◽  
Evidence Based Guidelines

Cancer immunotherapy based on the use of antibodies targeting the so-called checkpoint inhibitors, such as programmed cell death-1 receptor, its ligand, or CTLA-4, has shown durable clinical benefit and survival improvement in melanoma and other tumors. However, there are some special situations that could be a challenge for clinical management. Persons with chronic infections, such as HIV-1 or viral hepatitis, latent tuberculosis, or a history of solid organ transplantation, could be candidates for cancer immunotherapy, but their management requires a multidisciplinary approach. The Spanish Melanoma Group (GEM) panel in collaboration with experts in virology and immunology from different centers in Spain reviewed the literature and developed evidence-based guidelines for cancer immunotherapy management in patients with chronic infections and immunosuppression. These are the first clinical guidelines for cancer immunotherapy treatment in special challenging populations. Cancer immunotherapy in chronically infected or immunosuppressed patients is feasible but needs a multidisciplinary approach in order to decrease the risk of complications related to the coexistent comorbidities.

scholarly journals Estrogen/ER in anti-tumor immunity regulation to tumor cell and tumor microenvironment

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Tiecheng Wang ◽  
Jiakang Jin ◽  
Chao Qian ◽  
Jianan Lou ◽  
Jinti Lin ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Cancer Immunotherapy ◽  
Tumor Immunity ◽  
Immune Cells ◽  
Target Genes ◽  
Target Therapy ◽  
Treatment Strategies ◽  
Signal Transduction Pathway ◽  
Pathway Activation ◽  
Immune System Regulation

AbstractAs the essential sexual hormone, estrogen and its receptor has been proved to participate in the regulation of autoimmunity diseases and anti-tumor immunity. The adjustment of tumor immunity is related to the interaction between cancer cells, immune cells and tumor microenvironment, all of which is considered as the potential target in estrogen-induced immune system regulation. However, the specific mechanism of estrogen-induced immunity is poorly understood. Typically, estrogen causes the nuclear localization of estrogen/estrogen receptor complex and alternates the transcription pattern of target genes, leading to the reprogramming of tumor cells and differentiation of immune cells. However, the estrogen-induced non-canonical signal pathway activation is also crucial to the rapid function of estrogen, such as NF-κB, MAPK-ERK, and β-catenin pathway activation, which has not been totally illuminated. So, the investigation of estrogen modulatory mechanisms in these two manners is vital for the tumor immunity and can provide the potential for endocrine hormone targeted cancer immunotherapy. Here, this review summarized the estrogen-induced canonical and non-canonical signal transduction pathway and aimed to focus on the relationship among estrogen and cancer immunity as well as immune-related tumor microenvironment regulation. Results from these preclinical researches elucidated that the estrogen-target therapy has the application prospect of cancer immunotherapy, which requires the further translational research of these treatment strategies.

scholarly journals From Oncogenic Signaling Pathways to Single-Cell Sequencing of Immune Cells: Changing the Landscape of Cancer Immunotherapy

Molecules ◽  
2021 ◽  
Vol 26 (8) ◽  
pp. 2278
Author(s):  
Afshin Derakhshani ◽  
Zeinab Rostami ◽  
Hossein Safarpour ◽  
Mahdi Abdoli Shadbad ◽  
Niloufar Sadat Nourbakhsh ◽  
...  
Keyword(s):  
Single Cell ◽  
Signaling Pathways ◽  
Immune Cells ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Cancer Development ◽  
Immune Checkpoints ◽  
Single Cell Sequencing ◽  
Increased Risk

Over the past decade, there have been remarkable advances in understanding the signaling pathways involved in cancer development. It is well-established that cancer is caused by the dysregulation of cellular pathways involved in proliferation, cell cycle, apoptosis, cell metabolism, migration, cell polarity, and differentiation. Besides, growing evidence indicates that extracellular matrix signaling, cell surface proteoglycans, and angiogenesis can contribute to cancer development. Given the genetic instability and vast intra-tumoral heterogeneity revealed by the single-cell sequencing of tumoral cells, the current approaches cannot eliminate the mutating cancer cells. Besides, the polyclonal expansion of tumor-infiltrated lymphocytes in response to tumoral neoantigens cannot elicit anti-tumoral immune responses due to the immunosuppressive tumor microenvironment. Nevertheless, the data from the single-cell sequencing of immune cells can provide valuable insights regarding the expression of inhibitory immune checkpoints/related signaling factors in immune cells, which can be used to select immune checkpoint inhibitors and adjust their dosage. Indeed, the integration of the data obtained from the single-cell sequencing of immune cells with immune checkpoint inhibitors can increase the response rate of immune checkpoint inhibitors, decrease the immune-related adverse events, and facilitate tumoral cell elimination. This study aims to review key pathways involved in tumor development and shed light on single-cell sequencing. It also intends to address the shortcomings of immune checkpoint inhibitors, i.e., their varied response rates among cancer patients and increased risk of autoimmunity development, via applying the data from the single-cell sequencing of immune cells.

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