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 Mitotic quiescence in hepatic cancer stem cells: An incognito mode

2020 ◽  
Vol 14 (1) ◽  
Author(s):  
Kandasamy Ashokachakkaravarthy ◽  
Biju Pottakkat
Keyword(s):  
Hepatocellular Carcinoma ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cancer Cells ◽  
Immune Evasion ◽  
Immune Surveillance ◽  
Cancer Recurrence ◽  
Tumor Formation ◽  
Proliferating Cells ◽  
Recurrence Rates

Hepatocellular carcinoma represents one of the most aggressive cancers with high recurrence rates. The high recurrence is a major problem in the management of this disease. Cancer stem cells (CSCs) are often regarded as the basis of cancer recurrence. The anti-proliferative therapy kills the proliferating cells but induces mitotic quiescence in CSCs which remain as residual dormant CSCs. Later on, withdrawal of treatment reactivates the residual CSCs from dormancy to produce new cancer cells. The proliferation of these newly formed cancer cells initiates new tumor formation in the liver leading to tumor recurrence. HCC cells evade the immune surveillance via modulating the key immune cells by alpha feto-protein (AFP) secreted from CSCs or hepatic progenitor cells. This AFP mediated immune evasion assists in establishing new tumors by cancer cells in the liver. In this review, we will summarise the CSC mechanisms of recurrence, mitotic quiescence, dormancy and reactivation of CSCs, metastasis and immune evasion of hepatocellular carcinoma.

scholarly journals Cancer Stem Cells: Emerging Key Players in Immune Evasion of Cancers

2021 ◽  
Vol 9 ◽  
Author(s):  
Martina Mang Leng Lei ◽  
Terence Kin Wah Lee
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cancer Cells ◽  
Immune Cells ◽  
Immune Surveillance ◽  
Suppressor Cells ◽  
Tumor Infiltrating Lymphocytes ◽  
Treg Cells ◽  
Undifferentiated Cancer

Cancer stem cells (CSCs) are subpopulations of undifferentiated cancer cells within the tumor bulk that are responsible for tumor initiation, recurrence and therapeutic resistance. The enhanced ability of CSCs to give rise to new tumors suggests potential roles of these cells in the evasion of immune surveillance. A growing body of evidence has described the interplay between CSCs and immune cells within the tumor microenvironment (TME). Recent data have shown the pivotal role of some major immune cells in driving the expansion of CSCs, which concurrently elicit evasion of the detection and destruction of various immune cells through a number of distinct mechanisms. Here, we will discuss the role of immune cells in driving the stemness of cancer cells and provide evidence of how CSCs evade immune surveillance by exerting their effects on tumor-associated macrophages (TAMs), dendritic cells (DCs), myeloid-derived suppressor cells (MDSCs), T-regulatory (Treg) cells, natural killer (NK) cells, and tumor-infiltrating lymphocytes (TILs). The knowledge gained from the interaction between CSCs and various immune cells will provide insight into the mechanisms by which tumors evade immune surveillance. In conclusion, CSC-targeted immunotherapy emerges as a novel immunotherapy strategy against cancer by disrupting the interaction between immune cells and CSCs in the TME.

scholarly journals Concise review: The role of cancer-derived exosomes in tumorigenesis and immune cell modulation

2020 ◽  
Vol 7 (12) ◽  
pp. 4158-4169
Author(s):  
Nhi Thao Huynh ◽  
Khuong Duy Pham ◽  
Nhat Chau Truong
Keyword(s):  
Cancer Cells ◽  
Immune Cells ◽  
Immune Cell ◽  
Vascular System ◽  
Immune Surveillance ◽  
Cell Communication ◽  
Tumor Formation ◽  
Concise Review ◽  
The Relationship

Exosomes are subcellular entities which were first discovered in the 1980s. Over the past decade, scientists have discovered that they carry components of genetic information that allow for cell-cell communication and cell targeting. Exosomes secreted by cancer cells are termed cancer-derived exosomes (CDEs), and play an important role in tumor formation and progression. Specifically, CDEs mediate the communication between cancer cells, as well as between cancer cells and other cells in the tumor microenvironment, including cancer-associated fibroblasts, endothelial cells, mesenchymal stem cells, and effector immune cells. Additionally, through the vascular system and body fluids, CDEs can modulate response to drugs, increase angiogenesis, stimulate proliferation, promote invasion and metastasis, and facilitate escape from immune surveillance. This review will discuss the relationship between cancer cells and other cells (particularly immune cells), as mediated through CDEs, as well as the subsequent impact on tumorigenesis and immunomodulation. Understanding the role of CDEs in tumorigenesis and immune cell modulation will help advance their utilization in the diagnosis, prognosis, and treatment of cancer.

Role of the Immune Component of Tumor Microenvironment in the Efficiency of Cancer Treatment: Perspectives for the Personalized Therapy

2017 ◽  
Vol 23 (32) ◽  
pp. 4807-4826 ◽  
Author(s):  
Marina Stakheyeva ◽  
Vladimir Riabov ◽  
Irina Mitrofanova ◽  
Nikolai Litviakov ◽  
Evgeny Choynzonov ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Cancer Treatment ◽  
Cancer Cells ◽  
Solid Tumors ◽  
Immune Cells ◽  
Critical Factor ◽  
Cancer Diagnostics ◽  
Patient Specific ◽  
Intratumor Heterogeneity ◽  
Therapeutic Approaches

Despite significant progress in cancer diagnostics and development of novel therapeutic regimens, successful treatment of advanced forms of cancer is still a challenge and may require personalized therapeutic approaches. In this review, we analyzed major mechanisms responsible for tumor cells chemoresistance and emphasized that intratumor heterogeneity is a critical factor that limits efficiency of cancer treatment. Intratumor heterogeneity is caused by genomic instability in cancer cells, resulting in the selection of resistant clones. Moreover, cancer cells in solid tumors are surrounded by cellular and molecular microenvironment that actively influences tumor cell behavior. Local tumor microenvironment (TME) consisting of immune cells with diverse phenotypes and functions strongly contributes to intratumor heterogeneity and modulates responses to treatment. Thus, targeting specific components of TME is a novel treatment strategy that can improve the outcome of conventional anti-cancer therapy. Here, we discuss modern immunotherapeutic approaches based on targeting tumorinfiltrating immune cells including neutrophils, dendritic cells, NK cells, T cells, B cells and macrophages. Among those, tumor-associated macrophages (TAM) that display a pronounced heterogeneity and phenotypic plasticity appear to be a major component in the TME of solid tumors, and emerge as perspective targets for cancer immunotherapy. TAM intratumor heterogeneity and the possible existence of patient-specific phenotype signature generate the basis for the development of individualized TAM-based therapeutic approaches.

scholarly journals Platinum Derivatives Effects on Anticancer Immune Response

Biomolecules ◽  
2019 ◽  
Vol 10 (1) ◽  
pp. 13 ◽  
Author(s):  
Cédric Rébé ◽  
Lucie Demontoux ◽  
Thomas Pilot ◽  
François Ghiringhelli
Keyword(s):  
Immune Response ◽  
Cell Death ◽  
Immune Cells ◽  
Chemotherapeutic Agents ◽  
Immune Checkpoints ◽  
Immunogenic Cell Death ◽  
Host Immune System ◽  
Cytotoxic Effects ◽  
Cancer Types ◽  
Platinum Derivative

Along with surgery and radiotherapy, chemotherapeutic agents belong to the therapeutic arsenal in cancer treatment. In addition to their direct cytotoxic effects, these agents also impact the host immune system, which might enhance or counteract their antitumor activity. The platinum derivative compounds family, mainly composed of carboplatin, cisplatin and oxaliplatin, belongs to the chemotherapeutical arsenal used in numerous cancer types. Here, we will focus on the effects of these molecules on antitumor immune response. These compounds can induce or not immunogenic cell death (ICD), and some strategies have been found to induce or further enhance it. They also regulate immune cells’ fate. Platinum derivatives can lead to their activation. Additionally, they can also dampen immune cells by selective killing or inhibiting their activity, particularly by modulating immune checkpoints’ expression.

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.

scholarly journals An exploration of immunohistochemistry-based prognostic markers in patients undergoing curative resections for colon cancer

BMC Cancer ◽  
2022 ◽  
Vol 22 (1) ◽  
Author(s):  
Astrid Louise Bjørn Bennedsen ◽  
Luyi Cai ◽  
Rune Petring Hasselager ◽  
Aysun Avci Özcan ◽  
Khadra Bashir Mohamed ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Immune System ◽  
Cell Surface ◽  
Cancer Cells ◽  
Immune Cells ◽  
Cancer Recurrence ◽  
Surface Proteins ◽  
Recurrence Rates ◽  
Cell Surface Proteins ◽  
Cdx2 Expression

Abstract Background The immune system recognizes and destroys cancer cells. However, cancer cells develop mechanisms to avoid detection by expressing cell surface proteins. Specific tumour cell surface proteins (e.g. HLA-G, PD-L1, CDX2) either alone or in combination with the relative presence of immune cells (CD3 and CD8 positive T-cells) in the tumour tissue may describe the cancer cells’ ability to escape eradication by the immune system. The aim was to investigate the prognostic value of immunohistochemical markers in patients with colon cancer. Methods We conducted a retrospective study including patients diagnosed with pT3 and pT4 colon cancers. Immunohistochemical staining with HLA-G, PD-L1, CDX2, CD3, and CD8 was performed on tissue samples with representation of the invasive margin. PD-L1 expression in tumour cells and immune cells was reported conjointly. The expression of CD3 and CD8 was reported as a merged score based on the expression of both markers in the invasive margin and the tumour centre. Subsequently, a combined marker score was established based on all of the markers. Each marker added one point to the score when unfavourable immunohistochemical features was present, and the score was categorized as low, intermediate or high depending on the number of unfavourable stains. Hazard ratios for recurrence, disease-free survival and mortality were calculated. Results We included 188 patients undergoing colon cancer resections in 2011–2012. The median follow-up was 41.7 months, during which 41 (21.8%) patients had recurrence and 74 (39.4%) died. In multivariable regression analysis positive HLA-G expression (HR = 3.37, 95%CI [1.64–6.93]) was associated with higher recurrence rates, while a preserved CDX2 expression (HR = 0.23, 95%CI [0.06–0.85]) was associated with a lower risk of recurrence. An intermediate or high combined marker score was associated with increased recurrence rates (HR = 20.53, 95%CI [2.68–157.32] and HR = 7.56, 95%CI [1.06–54.16], respectively). Neither high expression of PD-L1 nor high CD3-CD8 score was significantly associated with recurrence rates. Patients with a high CD3-CD8 score had a significantly longer DFS and OS. Conclusions In tumour cells, expression of HLA-G and loss of CDX2 expression were associated with cancer recurrence. In addition, a combination of certain tumour tissue biomarkers was associated with colorectal cancer recurrence.

scholarly journals The force awakens: metastatic dormant cancer cells

2020 ◽  
Vol 52 (4) ◽  
pp. 569-581 ◽  
Author(s):  
So-Yeon Park ◽  
Jeong-Seok Nam
Keyword(s):  
Cancer Cells ◽  
Cancer Progression ◽  
Immune Cells ◽  
Immune Surveillance ◽  
Signaling Cascades ◽  
Diagnostic Systems ◽  
Cancer Proliferation ◽  
Recurrent Cancer ◽  
Cancer Dormancy ◽  
Extracellular Molecules

Abstract Recurrent cancer that spreads to distant sites is the leading cause of disease-related death among cancer patients. Cancer cells are likely to disseminate during cancer progression, and some may enter dormancy, remaining viable but not increasing. These dormant cancer cells (DCCs) are rarely detectable with current diagnostic systems. Moreover, they can interpret homoeostatic signals from the microenvironment, thereby evading immune surveillance and chemotherapy. Eventually, DCCs can reawaken in response to signals, which are not yet fully understood, resulting in recurrence and metastasis. Therefore, understanding the biology of DCC reawakening is key to preventing metastasis. Over the last decade, a growing body of literature has revealed the mechanisms involved in cancer dormancy and reawakening. The cytotoxic activity of immune cells can cause cancer cells to enter a dormant state, and chronic inflammation can reactivate cancer proliferation at distant sites. Upon the binding of circulating DCCs to extracellular molecules, various signaling cascades are activated and reinitiate cell proliferation. In the present review, we attempt to consolidate the existing literature to provide a framework for the understanding of this crucial step in cancer progression.

scholarly journals Understanding the Reciprocal Interplay Between Antibiotics and Host Immune System: How Can We Improve the Anti-Mycobacterial Activity of Current Drugs to Better Control Tuberculosis?

2021 ◽  
Vol 12 ◽  
Author(s):  
Hyun-Eui Park ◽  
Wonsik Lee ◽  
Min-Kyoung Shin ◽  
Sung Jae Shin
Keyword(s):  
Immune System ◽  
Immune Cells ◽  
Multidrug Resistant ◽  
Antimicrobial Activities ◽  
Host Immune System ◽  
Therapeutic Approaches ◽  
Host Immune Responses ◽  
Tb Treatment ◽  
Immune Mediators ◽  
Immune Mediated

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb) infection, remains a global health threat despite recent advances and insights into host-pathogen interactions and the identification of diverse pathways that may be novel therapeutic targets for TB treatment. In addition, the emergence and spread of multidrug-resistant Mtb strains led to a low success rate of TB treatments. Thus, novel strategies involving the host immune system that boost the effectiveness of existing antibiotics have been recently suggested to better control TB. However, the lack of comprehensive understanding of the immunomodulatory effects of anti-TB drugs, including first-line drugs and newly introduced antibiotics, on bystander and effector immune cells curtailed the development of effective therapeutic strategies to combat Mtb infection. In this review, we focus on the influence of host immune-mediated stresses, such as lysosomal activation, metabolic changes, oxidative stress, mitochondrial damage, and immune mediators, on the activities of anti-TB drugs. In addition, we discuss how anti-TB drugs facilitate the generation of Mtb populations that are resistant to host immune response or disrupt host immunity. Thus, further understanding the interplay between anti-TB drugs and host immune responses may enhance effective host antimicrobial activities and prevent Mtb tolerance to antibiotic and immune attacks. Finally, this review highlights novel adjunctive therapeutic approaches against Mtb infection for better disease outcomes, shorter treatment duration, and improved treatment efficacy based on reciprocal interactions between current TB antibiotics and host immune cells.

Cytotoxic effects of disulfiram and synergism with cisplatin on ovarian cancer cells in vitro

2018 ◽  
Author(s):  
F Guo ◽  
Z Yang ◽  
J Xu ◽  
J Sehouli ◽  
AE Albers ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Ovarian Cancer Cells ◽  
Cytotoxic Effects
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