Avoidance of Cancer Cell Destruction by the Immune System

Author(s):  
L. de la Cruz-Merino ◽  
A. Illescas-Vacas ◽  
R. Sánchez-Escribano
2021 ◽  
pp. 2000145
Author(s):  
Sreejith Raveendran ◽  
Anindito Sen ◽  
Toru Maekawa ◽  
D. Sakthi Kumar

Author(s):  
Madheswaran Suresh ◽  
Malarvizhi Gurusamy ◽  
Natarajan Sudhakar

<p>Immune surveillance is a mechanism where cells and tissues are watched constantly by ever alerted immune system. Most incipient cancer cells are recognized and eliminated by the immune surveillance mechanism, but still tumors have the ability to evade immune surveillance and immunological killing. One greater arm that tumor use to evade immune surveillance, is by expressing anti-phagocytic signal (CD47). Here we present a provocative hypothesis where cancer cells are removed alive by phagocytic cell (DC). That in turn will elicit effective and higher immunogenic condition. All this could be possible by addition pro-phagocytic signal (PtdSer) over cancer cell surface (Breast Cancer), that mask the presence of anti-phagocytic signal (CD47). In other words, adding eat me signal (PtdSer) over the breast cancer cell surface that mask the presence of don’t eat me signal or anti-phagocytic signal present in breast cancer cell surface. This could be possible by using bi-specific antibody, conjugated to PEG-modified liposomes, which carry (PtdSer) pro-phagocytic signal (or) eat me signal, which target both CD47 and EGFRVIII on breast carcinoma. The simultaneous masking of anti-phagocytic signal, and adding of pro–phagocytic signal over cancer cell, will enhance the phagocytic clearance of live tumor cell and elicit immunological killing.</p>


2019 ◽  
Author(s):  
Wenfa Ng

The immune checkpoint plays an important role in keeping immune cells in check for protecting tissues and organs from attack by the body’s own immune system. Similar concepts also apply in how cancer cells managed to fool immune cells through the surface display of particular antigens that mimic those exhibited by normal body cells. Specifically, cancer cells display antigens that bind to receptors on immune cells that subsequently prevent an attack on the cancer cells. Such binding between cancer antigens and immune cell receptors can be prevented through the use of checkpoint inhibitors antibodies specific for particular receptors on immune cells; thereby, unleashing immune cells to mount an immune response against cancer cells. While demonstrating good remissions in many patients where tumours shrunk substantially after administration of checkpoint inhibitors, cases exist where an overactivated immune system cause harm to organs and tissues culminating in multiple organ failure. Analysis of such toxicity effects of checkpoint inhibitors revealed that generic nature of targeted immune receptor plays a pivotal role in determining extent of side effects. Specifically, if the target immune receptor participates in checkpoints that prevent immune cells from attacking host cells, unleashing such receptors in cancer therapy may have untoward effects on patient’s health. Hence, the goal should be the selection of immune cell receptor specific to cancer cell antigens and which does not bind antigens or ligands displayed by the body’s cells. Such receptors would provide ideal targets for the development of checkpoint inhibitor antibodies for unleashing immune cells against cancer cells. To search for non-generic receptors that bind cancer cell antigens only, a combined computational and experimental approach could be used where ensemble of surface antigens on cancer cells and available receptors on immune cells could be profiled by biochemical assays. Downstream purification of ligands and receptors would provide for both structural elucidation and amino acid sequencing useful for bioinformatic search of homologous sequences. Knowledge of the antigens’ and receptors’ structures and amino acid sequence would subsequently serve as inputs to computational algorithms that models molecular docking events between receptor and antigen. This paves the way for heterologous expression of putative ligand and receptor in cell lines cultured in co-culture format for assessing binding between ligand and receptor, and more importantly, its physiological effects. Ability of immune receptor to bind to ligands on normal cells could also be assessed. Similar co-culture studies could be conducted with cancer cells and different immune cell types to check for reproducibility of observed effect in cell lines. Finally, antibodies could be raised for candidate receptors whose inhibition would not result in systemic attack of immune cells on host cells.


2016 ◽  
Vol 1865 (2) ◽  
pp. 168-175 ◽  
Author(s):  
Fernando Mendes ◽  
Cátia Domingues ◽  
Paulo Rodrigues-Santos ◽  
Ana Margarida Abrantes ◽  
Ana Cristina Gonçalves ◽  
...  
Keyword(s):  

2014 ◽  
Vol 10 (2) ◽  
pp. 831-842 ◽  
Author(s):  
Wei Rao ◽  
Wujie Zhang ◽  
Izmarie Poventud-Fuentes ◽  
Yongchen Wang ◽  
Yifeng Lei ◽  
...  

2021 ◽  
Vol 2021 ◽  
pp. 1-19
Author(s):  
Fatemeh Faramarzi ◽  
Parisa Zafari ◽  
Mina Alimohammadi ◽  
Mohammadreza Moonesi ◽  
Alireza Rafiei ◽  
...  

Despite recent advances in therapy, cancer still is a devastating and life-threatening disease, motivating novel research lines in oncology. Cold physical plasma, a partially ionized gas, is a new modality in cancer research. Physical plasma produces various physicochemical factors, primarily reactive oxygen and nitrogen species (ROS/RNS), causing cancer cell death when supplied at supraphysiological concentrations. This review outlines the biomedical consequences of plasma treatment in experimental cancer therapy, including cell death modalities. It also summarizes current knowledge on intracellular signaling pathways triggered by plasma treatment to induce cancer cell death. Besides the inactivation of tumor cells, an equally important aspect is the inflammatory context in which cell death occurs to suppress or promote the responses of immune cells. This is mainly governed by the release of damage-associated molecular patterns (DAMPs) to provoke immunogenic cancer cell death (ICD) that, in turn, activates cells of the innate immune system to promote adaptive antitumor immunity. The pivotal role of the immune system in cancer treatment, in general, is highlighted by many clinical trials and success stories on using checkpoint immunotherapy. Hence, the potential of plasma treatment to induce ICD in tumor cells to promote immunity targeting cancer lesions systemically is also discussed.


2019 ◽  
Author(s):  
Wenfa Ng

The immune checkpoint plays an important role in keeping immune cells in check for protecting tissues and organs from attack by the body’s own immune system. Similar concepts also apply in how cancer cells managed to fool immune cells through the surface display of particular antigens that mimic those exhibited by normal body cells. Specifically, cancer cells display antigens that bind to receptors on immune cells that subsequently prevent an attack on the cancer cells. Such binding between cancer antigens and immune cell receptors can be prevented through the use of checkpoint inhibitors antibodies specific for particular receptors on immune cells; thereby, unleashing immune cells to mount an immune response against cancer cells. While demonstrating good remissions in many patients where tumours shrunk substantially after administration of checkpoint inhibitors, cases exist where an overactivated immune system cause harm to organs and tissues culminating in multiple organ failure. Analysis of such toxicity effects of checkpoint inhibitors revealed that generic nature of targeted immune receptor plays a pivotal role in determining extent of side effects. Specifically, if the target immune receptor participates in checkpoints that prevent immune cells from attacking host cells, unleashing such receptors in cancer therapy may have untoward effects on patient’s health. Hence, the goal should be the selection of immune cell receptor specific to cancer cell antigens and which does not bind antigens or ligands displayed by the body’s cells. Such receptors would provide ideal targets for the development of checkpoint inhibitor antibodies for unleashing immune cells against cancer cells. To search for non-generic receptors that bind cancer cell antigens only, a combined computational and experimental approach could be used where ensemble of surface antigens on cancer cells and available receptors on immune cells could be profiled by biochemical assays. Downstream purification of ligands and receptors would provide for both structural elucidation and amino acid sequencing useful for bioinformatic search of homologous sequences. Knowledge of the antigens’ and receptors’ structures and amino acid sequence would subsequently serve as inputs to computational algorithms that models molecular docking events between receptor and antigen. This paves the way for heterologous expression of putative ligand and receptor in cell lines cultured in co-culture format for assessing binding between ligand and receptor, and more importantly, its physiological effects. Ability of immune receptor to bind to ligands on normal cells could also be assessed. Similar co-culture studies could be conducted with cancer cells and different immune cell types to check for reproducibility of observed effect in cell lines. Finally, antibodies could be raised for candidate receptors whose inhibition would not result in systemic attack of immune cells on host cells.


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