Ecology of Fear: Spines, Armor and Noxious Chemicals Deter Predators in Cancer and in Nature

In nature, many multicellular and unicellular organisms use constitutive defenses such as armor, spines, and noxious chemicals to keep predators at bay. These defenses render the prey difficult and/or dangerous to subdue and handle, which confers a strong deterrent for predators. The distinct benefit of this mode of defense is that prey can defend in place and continue activities such as foraging even under imminent threat of predation. The same qualitative types of armor-like, spine-like, and noxious defenses have evolved independently and repeatedly in nature, and we present evidence that cancer is no exception. Cancer cells exist in environments inundated with predator-like immune cells, so the ability of cancer cells to defend in place while foraging and proliferating would clearly be advantageous. We argue that these defenses repeatedly evolve in cancers and may be among the most advanced and important adaptations of cancers. By drawing parallels between several taxa exhibiting armor-like, spine-like, and noxious defenses, we present an overview of different ways these defenses can appear and emphasize how phenotypes that appear vastly different can nevertheless have the same essential functions. This cross-taxa comparison reveals how cancer phenotypes can be interpreted as anti-predator defenses, which can facilitate therapy approaches which aim to give the predators (the immune system) the upper hand. This cross-taxa comparison is also informative for evolutionary ecology. Cancer provides an opportunity to observe how prey evolve in the context of a unique predatory threat (the immune system) and varied environments.

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Amoebic Foraging Model of Metastatic Cancer Cells

Symmetry ◽

10.3390/sym13071140 ◽

2021 ◽

Vol 13 (7) ◽

pp. 1140

Author(s):

Daiki Andoh ◽

Yukio-Pegio Gunji

Keyword(s):

Bayesian Inference ◽

Cancer Cells ◽

Metastatic Cancer ◽

Gait Patterns ◽

Lévy Walk ◽

Levy Walk ◽

Unicellular Organisms ◽

Living Organisms ◽

Walk Algorithm ◽

Metastatic Cancer Cells

The Lévy walk is a pattern that is often seen in the movement of living organisms; it has both ballistic and random features and is a behavior that has been recognized in various animals and unicellular organisms, such as amoebae, in recent years. We proposed an amoeba locomotion model that implements Bayesian and inverse Bayesian inference as a Lévy walk algorithm that balances exploration and exploitation, and through a comparison with general random walks, we confirmed its effectiveness. While Bayesian inference is expressed only by P(h) = P(h|d), we introduce inverse Bayesian inference expressed as P(d|h) = P(d) in a symmetry fashion. That symmetry contributes to balancing contracting and expanding the probability space. Additionally, the conditions of various environments were set, and experimental results were obtained that corresponded to changes in gait patterns with respect to changes in the conditions of actual metastatic cancer cells.

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Why Target Innate Immune Cells in Cancers?

Cancers ◽

10.3390/cancers13040690 ◽

2021 ◽

Vol 13 (4) ◽

pp. 690

Author(s):

Mary Poupot

Keyword(s):

Immune System ◽

Cancer Cells ◽

Immune Cells ◽

Innate Immune ◽

Innate Immune Cells

The immune system is a smart way to fight cancer, with its precise targeting of cancer cells sparing healthy cells [...]

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An Efficient Photodynamic Therapy Treatment for Human Pancreatic Adenocarcinoma

Journal of Clinical Medicine ◽

10.3390/jcm9010192 ◽

2020 ◽

Vol 9 (1) ◽

pp. 192 ◽

Cited By ~ 5

Author(s):

Alexandre Quilbe ◽

Olivier Moralès ◽

Martha Baydoun ◽

Abhishek Kumar ◽

Rami Mustapha ◽

...

Keyword(s):

Pancreatic Cancer ◽

Photodynamic Therapy ◽

Immune System ◽

Cancer Cells ◽

Pancreatic Adenocarcinoma ◽

Cell Lines ◽

Folate Receptor ◽

Mice Model ◽

Gene And Protein Expression ◽

The Impact

To date, pancreatic adenocarcinoma (ADKP) is a devastating disease for which the incidence rate is close to the mortality rate. The survival rate has evolved only 2–5% in 45 years, highlighting the failure of current therapies. Otherwise, the use of photodynamic therapy (PDT), based on the use of an adapted photosensitizer (PS) has already proved its worth and has prompted a growing interest in the field of oncology. We have developed a new photosensitizer (PS-FOL/PS2), protected by a recently published patent (WO2019 016397-A1, 24 January 2019). This photosensitizer is associated with an addressing molecule (folic acid) targeting the folate receptor 1 (FOLR1) with a high affinity. Folate binds to FOLR1, in a specific way, expressed in 100% of ADKP or over-expressed in 30% of cases. The first objective of this study is to evaluate the effectiveness of this PS2-PDT in four ADKP cell lines: Capan-1, Capan-2, MiapaCa-2, and Panc-1. For this purpose, we first evaluated the gene and protein expression of FOLR1 on four ADKP cell lines. Subsequently, we evaluated PS2’s efficacy in our cell lines and we assessed the impact of PDT on the secretome of cancer cells and its impact on the immune system. Finally, we evaluate the PDT efficacy on a humanized SCID mouse model of pancreatic cancer. In a very interesting way, we observed a significant increase in the proliferation of activated-human PBMC when cultured with conditioned media of ADKP cancer cells subjected to PDT. Furthermore, to evaluate in vivo the impact of this new PS, we analyzed the tumor growth in a humanized SCID mice model of pancreatic cancer. Four conditions were tested: Untreated, mice (nontreated), mice with PS (PS2), mice subjected to illumination (Light only), and mice subjected to illumination in the presence of PS (PDT). We noticed that the mice subjected to PDT presented a strong decrease in the growth of the tumor over time after illumination. Our investigations have not only suggested that PS2-PDT is an effective therapy in the treatment of PDAC but also that it activates the immune system and could be considered as a real adjuvant for anti-cancer vaccination. Thus, this new study provides new treatment options for patients in a therapeutic impasse and will provide a new arsenal in the fight against PDAC.

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The Role of Sphingolipids in Cancer Immunotherapy

International Journal of Molecular Sciences ◽

10.3390/ijms22126492 ◽

2021 ◽

Vol 22 (12) ◽

pp. 6492

Author(s):

Paola Giussani ◽

Alessandro Prinetti ◽

Cristina Tringali

Keyword(s):

Immune System ◽

Cancer Cells ◽

Immune Cells ◽

Plasma Membranes ◽

Checkpoint Inhibitors ◽

Surface Receptors ◽

Car T ◽

Sphingosine 1 Phosphate ◽

And Migration ◽

Lymphocyte Egress

Immunotherapy is now considered an innovative and strong strategy to beat metastatic, drug-resistant, or relapsing tumours. It is based on the manipulation of several mechanisms involved in the complex interplay between cancer cells and immune system that culminates in a form of immune-tolerance of tumour cells, favouring their expansion. Current immunotherapies are devoted enforcing the immune response against cancer cells and are represented by approaches employing vaccines, monoclonal antibodies, interleukins, checkpoint inhibitors, and chimeric antigen receptor (CAR)-T cells. Despite the undoubted potency of these treatments in some malignancies, many issues are being investigated to amplify the potential of application and to avoid side effects. In this review, we discuss how sphingolipids are involved in interactions between cancer cells and the immune system and how knowledge in this topic could be employed to enhance the efficacy of different immunotherapy approaches. In particular, we explore the following aspects: how sphingolipids are pivotal components of plasma membranes and could modulate the functionality of surface receptors expressed also by immune cells and thus their functionality; how sphingolipids are related to the release of bioactive mediators, sphingosine 1-phosphate, and ceramide that could significantly affect lymphocyte egress and migration toward the tumour milieu, in addition regulating key pathways needed to activate immune cells; given the renowned capability of altering sphingolipid expression and metabolism shown by cancer cells, how it is possible to employ sphingolipids as antigen targets.

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The importance of cancer cells for animal evolutionary ecology

Nature Ecology & Evolution ◽

10.1038/s41559-017-0343-z ◽

2017 ◽

Vol 1 (11) ◽

pp. 1592-1595 ◽

Cited By ~ 23

Author(s):

Frédéric Thomas ◽

Camille Jacqueline ◽

Tazzio Tissot ◽

Morgane Henard ◽

Simon Blanchet ◽

...

Keyword(s):

Cancer Cells ◽

Evolutionary Ecology

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Cancer immunoediting: A game theoretical approach

In Silico Biology ◽

10.3233/isb-200475 ◽

2020 ◽

pp. 1-12

Author(s):

Fatemeh Tavakoli ◽

Javad Salimi Sartakhti ◽

Mohammad Hossein Manshaei ◽

David Basanta

Keyword(s):

Immune System ◽

Cancer Cells ◽

Evolutionary Game ◽

Equilibrium Phase ◽

Tumor Development ◽

Treatment Strategies ◽

Cancer Immunoediting ◽

Proposed Model ◽

Game Theoretical Approach ◽

First Time

The role of the immune system in tumor development increasingly includes the idea of cancer immunoediting. It comprises three phases: elimination, equilibrium, and escape. In the first phase, elimination, transformed cells are recognized and destroyed by immune system. The rare tumor cells that are not destroyed in this phase may then enter the equilibrium phase, where their growth is prevented by immunity mechanisms. The escape phase represents the final phase of this process, where cancer cells begin to grow unconstrained by the immune system. In this study, we describe and analyze an evolutionary game theoretical model of proliferating, quiescent, and immune cells interactions for the first time. The proposed model is evaluated with constant and dynamic approaches. Population dynamics and interactions between the immune system and cancer cells are investigated. Stability of equilibria or critical points are analyzed by applying algebraic analysis. This model allows us to understand the process of cancer development and might help us design better treatment strategies to account for immunoediting.

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MASKING ANTI-PHAGOCYTIC SIGNAL OF TUMOR BY PRO-PHAGOCYTIC SIGNAL-A KEY TO IMMUREMENT OF CANCER CELL

International Journal of Pharmacy and Pharmaceutical Sciences ◽

10.22159/ijpps.2016v8i9.12990 ◽

2016 ◽

Vol 8 (9) ◽

pp. 323

Author(s):

Madheswaran Suresh ◽

Malarvizhi Gurusamy ◽

Natarajan Sudhakar

Keyword(s):

Breast Cancer ◽

Immune System ◽

Breast Carcinoma ◽

Cell Surface ◽

Cancer Cells ◽

Cancer Cell ◽

Breast Cancer Cell ◽

Immune Surveillance ◽

Phagocytic Cell ◽

Surveillance Mechanism

<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>

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Search for receptors in immune cells that bind cancer cell antigens and their activation in silent cases

10.7287/peerj.preprints.27670 ◽

2019 ◽

Author(s):

Wenfa Ng

Keyword(s):

Immune System ◽

Amino Acid ◽

Cancer Cells ◽

Cell Lines ◽

Cancer Cell ◽

Immune Cells ◽

Immune Cell ◽

Checkpoint Inhibitors ◽

Host Cells ◽

Immune Receptor

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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