• Biomolecules & Therapeutics
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• v.32 no.1
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• pp.13-24
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• 2024

Cytokines influence the overall cancer immune cycle by triggering tumor antigen expression, antigen presenting, immune cell priming and activation, effector immune cell recruitment and infiltration to cancer, and cancer killing in the tumor microenvironment (TME). Therefore, cytokines have been considered potential anti-cancer immunotherapy, and cytokine-based anti-cancer therapies continue to be an active area of research and development in the field of cancer immunotherapy, with ongoing clinical trials exploring new strategies to improve efficacy and safety. In this review, we examine past and present clinical developments for major anticancer cytokines, including interleukins (IL-2, IL-15, IL-12, IL-21), interferons, TGF-beta, and GM-CSF. We identify the current status and changes in the technology platform being applied to cytokine-based immune anti-cancer therapeutics. Through this, we discuss the opportunities and challenges of cytokine-based immune anti-cancer treatments in the current immunotherapy market and suggest development directions to enhance the clinical use of cytokines as immuno-anticancer drugs in the future.

• Biomaterials Research
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• v.22 no.4
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• pp.211-220
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• 2018

Background: Recently, cancer immunotherapy has become standard for cancer treatment. Immunotherapy not only treats primary tumors, but also prevents metastasis and recurrence, representing a major advantage over conventional cancer treatments. However, existing cancer immunotherapies have limited clinical benefits because cancer antigens are often not effectively delivered to immune cells. Furthermore, unlike lymphoma, solid tumors evade anti-cancer immunity by forming an immune-suppressive tumor microenvironment (TME). One approach for overcoming these limitations of cancer immunotherapy involves nanoparticles based on biomaterials. Main body: Here, we review in detail recent trends in the use of nanoparticles in cancer immunotherapy. First, to illustrate the unmet needs for nanoparticles in this field, we describe the mechanisms underlying cancer immunotherapy. We then explain the role of nanoparticles in the delivery of cancer antigens and adjuvants. Next, we discuss how nanoparticles can be helpful within the immune-suppressive TME. Finally, we summarize current and future uses of nanoparticles with image-guided interventional techniques in cancer immunotherapy. Conclusion: Recently developed approaches for using nanoparticles in cancer immunotherapy have enormous potential for improving cancer treatment. Cancer immunotherapy based on nanoparticles is anticipated not only to overcome the limitations of existing immunotherapy, but also to generate synergistic effects via cooperation between nanoparticles and immune cells.

• Journal of Digestive Cancer Research
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• v.6 no.2
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• pp.45-49
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• 2018

Colorectal cancer (CRC) is the third most common cause of cancer-related death in the world. Although the long-term outcome of patients with metastatic CRC is still poor, target therapy including anti EGFR agents and anti VEGF agents and immunotherapy including anti PD-1 antibody and anti CTLA-4 antibody have shown clinical benefits in the treatment of patient with metastatic CRC. In the future, the personalized treatment strategy based on the clinical characteristics and biologic features of patients with metastatic CRC will be necessary. In this review, we summarized the mechanisms and clinical evidences of target therapy and immunotherapy, and the guideline of clinical practice in patients with metastatic CRC.

• BMB Reports
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• v.53 no.10
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• pp.512-520
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• 2020

T-cell-based cancer immunotherapies, such as immune checkpoint blockers (ICBs) and chimeric antigen receptor (CAR)-T-cells, have significant anti-tumor effects against certain types of cancer, providing a new paradigm for cancer treatment. However, the activity of tumor infiltrating T-cells (TILs) can be effectively neutralized in the tumor microenvironment (TME) of most solid tumors, rich in various immunosuppressive factors and cells. Therefore, to improve the clinical outcomes of established T-cell-based immunotherapy, adjuvants that can comprehensively relieve multiple immunosuppressive mechanisms of TME are needed. In this regard, recent studies have revealed that metformin has several beneficial effects on anti-tumor immunity. In this mini-review, we understand the immunosuppressive properties of TME and how metformin comprehensively enhances anti-tumor immunity. Finally, we will discuss this old friend's potential as an adjuvant for cancer immunotherapy.

• Biomedical Science Letters
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• v.29 no.4
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• pp.382-385
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• 2023

NK (Natural killer) cells are innate immune cells and play important roles as the first immune cells to act when cancer occurs. In many cancer patients, NK cells can be seen to be inactivated, suggesting that NK cells are important in cancer treatment. In order to overcome the disadvantages of NK cells in cancer treatment, it is critical to develop strategies that enhance the proliferation and cytolytic function of NK cells. We applied niclosamide to measure the degree of NK cell activation, and obtained unexpected results of increased NK cell numbers and anti-tumor activity. Although further investigation is required to uncover the detailed mechanisms, our results suggest that Niclosamide is a promising candidate to increase the efficacy of cancer immunotherapy using NK cells.

• IMMUNE NETWORK
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• v.14 no.6
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• pp.265-276
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• 2014

The interactions between B7 molecules and CD28-family receptors are crucial in the regulation of adaptive cellular immunity. In cancer, the aberrant expression of co-inhibitory B7 molecules has been attributed to reduced anti-tumor immunity and cancer immune evasion, prompting the development of cancer therapeutics that can restore T cell function. Murine tumor models have provided significant support for the targeting of multiple immune checkpoints involving CTLA-4, PD-1, ICOS, B7-H3 and B7-H4 during tumor growth, and clinical studies investigating the therapeutic effects of CTLA-4 and PD-1 blockade have shown exceptionally promising results in patients with advanced melanoma and other cancers. The expression pattern of co-inhibitory B7 ligands in the tumor microenvironment has also been largely correlated with poor patient prognosis, and recent evidence suggests that the presence of several B7 molecules may predict the responsiveness of immunotherapies that rely on pre-existing tumor-associated immune responses. While monotherapies blocking T cell co-inhibition have beneficial effects in reducing tumor burden, combinatorial immunotherapy targeting multiple immune checkpoints involved in various stages of the anti-tumor response has led to the most substantial impact on tumor reduction. In this review, we will examine the contributions of B7- and CD28-family members in the context of cancer development, and discuss the implications of current human findings in cancer immunotherapy.

• Journal of Microbiology and Biotechnology
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• v.32 no.9
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• pp.1086-1097
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• 2022

During the last decades, research and therapeutic methods in cancer treatment have been evolving. As the results, nowadays, cancer patients are receiving several types of treatments, ranging from chemotherapy and radiation therapy to surgery and immunotherapy. In fact, most cancer patients take a combination of current anti-cancer therapies to improve the efficacy of treatment. However, current strategies still cause some side effects to patients, such as pain and depression. Therefore, there is the need to discover better ways to eradicate cancer whilst minimizing side effects. Recently, immunotherapy, particularly immune checkpoint blockade, is rising as an effective anti-cancer treatment. Unlike chemotherapy or radiation therapy, immunotherapy has few side effects and a higher tumor cell removal efficacy depend on cellular immunological mechanisms. Moreover, recent studies suggest that tissue immune responses are regulated by their microbiome composition. Each tissue has their specific microenvironment, which makes their microbiome composition different, particularly in the context of different types of cancer, such as breast, colorectal, kidney, lung, and skin. Herein, we review the current understanding of the relationship of immune responses and tissue microbiome in cancer in both animal and human studies. Moreover, we discuss the cancer-microbiome-immune axis in the context of cancer development and treatment. Finally, we speculate on strategies to control tissue microbiome alterations that may synergistically affect the immune system and impact cancer treatment outcomes.

• IMMUNE NETWORK
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• v.24 no.1
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• pp.5.1-5.19
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• 2024

The key role of T cells in cancer immunotherapy is well established and is highlighted by the remarkable capacity of Ab-mediated checkpoint blockade to overcome T-cell exhaustion and amplify anti-tumor responses. However, total or partial tumor remission following checkpoint blockade is still limited to only a few types of tumors. Hence, concerted attempts are being made to devise new methods for improving tumor immunity. Currently, much attention is being focused on therapy with IL-2. This cytokine is a powerful growth factor for T cells and optimises their effector functions. When used at therapeutic doses for cancer treatment, however, IL-2 is highly toxic. Nevertheless, recent work has shown that modifying the structure or presentation of IL-2 can reduce toxicity and lead to effective anti-tumor responses in synergy with checkpoint blockade. Here, we review the complex interaction of IL-2 with T cells: first during normal homeostasis, then during responses to pathogens, and finally in anti-tumor responses.

• IMMUNE NETWORK
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• v.20 no.1
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• pp.3.1-3.20
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• 2020

Immune checkpoint inhibitors (ICIs), including anti-PD-1 and anti-CTLA-4 therapeutic agents, are now approved by the Food and Drug Administration for treatment of various types of cancer. However, the therapeutic efficacy of ICIs varies among patients and cancer types. Moreover, most patients do not develop durable antitumor responses after ICI therapy due to an ephemeral reversal of T-cell dysfunction. As co-stimulatory receptors play key roles in regulating the effector functions of T cells, activating co-stimulatory pathways may improve checkpoint inhibition efficacy, and lead to durable antitumor responses. Here, we review recent advances in our understating of co-stimulatory receptors in cancers, providing the necessary groundwork for the rational design of cancer immunotherapy.

• BMB Reports
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• v.56 no.5
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• pp.275-286
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• 2023

Cancer immunotherapy has been acknowledged as a new paradigm for cancer treatment, with notable therapeutic effects on certain cancer types. Despite their significant potential, clinical studies over the past decade have revealed that cancer immunotherapy has low response rates in the majority of solid tumors. One of the key causes for poor responses is known to be the relatively low immunogenicity of solid tumors. Because most solid tumors are immune desert 'cold tumors' with antitumor immunity blocked from the onset of innate immunity, combination therapies that combine validated T-based therapies with approaches that can increase tumor-immunogenicity are being considered as relevant therapeutic options. This review paper focuses on immunogenic cell death (ICD) as a way of enhancing immunogenicity in tumor tissues. We will thoroughly review how ICDs such as necroptosis, pyroptosis, and ferroptosis can improve anti-tumor immunity and outline clinical trials targeting ICD. Finally, we will discuss the potential of ICD inducers as an adjuvant for cancer immunotherapy.