The Immune System and Responses to Cancer: Coordinated Evolution

This review explores the incessant evolutionary interaction and co-development between immune system evolution and somatic evolution, to put it into context with the short, over 60-year, detailed human study of this extraordinary protective system. Over millions of years, the evolutionary development of the immune system in most species has been continuously shaped by environmental interactions between microbes, and aberrant somatic cells, including malignant cells. Not only has evolution occurred in somatic cells to adapt to environmental pressures for survival purposes, but the immune system and its function has been successively shaped by those same evolving somatic cells and microorganisms through continuous adaptive symbiotic processes of progressive simultaneous immunological and somatic change to provide what we observe today. Indeed, the immune system as an environmental influence has also shaped somatic and microbial evolution. Although the immune system is tuned to primarily controlling microbiological challenges for combatting infection, it can also remove damaged and aberrant cells, including cancer cells to induce long-term cures. Our knowledge of how this occurs is just emerging. Here we consider the connections between immunity, infection and cancer, by searching back in time hundreds of millions of years to when multi-cellular organisms first began. We are gradually appreciating that the immune system has evolved into a truly brilliant and efficient protective mechanism, the importance of which we are just beginning to now comprehend. Understanding these aspects will likely lead to more effective cancer and other therapies.

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The Immune System and Responses to Cancer: Coordinated Evolution

F1000Research ◽

10.12688/f1000research.6718.2 ◽

2020 ◽

Vol 4 ◽

pp. 552

Author(s):

Brendon J. Coventry ◽

Martin Ashdown ◽

Maciej Henneberg

Keyword(s):

Immune System ◽

Environmental Influence ◽

Somatic Cells ◽

Human Study ◽

Microbial Evolution ◽

Evolutionary Development ◽

Protective Mechanism ◽

Environmental Pressures ◽

Immune System Evolution ◽

Somatic Evolution

This review explores the incessant evolutionary interaction and co-development between immune system evolution and somatic evolution, to put it into context with the short, over 60-year, detailed human study of this extraordinary protective system. Over millions of years, the evolutionary development of the immune system in most species has been continuously shaped by environmental interactions between microbes, and aberrant somatic cells, including malignant cells. Not only has evolution occurred in somatic cells to adapt to environmental pressures for survival purposes, but the immune system and its function has been successively shaped by those same evolving somatic cells and microorganisms through continuous adaptive symbiotic processes of progressive simultaneous immunological and somatic change to provide what we observe today. Indeed, the immune system as an environmental influence has also shaped somatic and microbial evolution. Although the immune system is tuned to primarily controlling microbiological challenges for combatting infection, it can also remove damaged and aberrant cells, including cancer cells to induce long-term cures. Our knowledge of how this occurs is just emerging. Here we consider the connections between immunity, infection and cancer, by searching back in time hundreds of millions of years to when multi-cellular organisms first began. We are gradually appreciating that the immune system has evolved into a truly brilliant and efficient protective mechanism, the importance of which we are just beginning to now comprehend. Understanding these aspects will likely lead to more effective cancer and other therapies.

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Infiltration of immune competent cells into primary tumors and their surrounding connective tissues in mice

10.21203/rs.3.rs-31564/v1 ◽

2020 ◽

Author(s):

Marlon Metzen ◽

Michael Bruns ◽

Wolfgang Deppert ◽

Udo Schumacher

Keyword(s):

Lung Cancer ◽

Dendritic Cells ◽

Adipose Tissue ◽

Immune System ◽

Cancer Cells ◽

Tumor Stroma ◽

Small Cell ◽

Malignant Cells ◽

Small Cell Lung ◽

Tumor Capsule

Abstract Background: Due to the fact that a close physical contact between NK- and T-cells and cancer cells themselves is necessary to kill cancer cells, we wanted to study the distribution of immunocompetent cells in syngeneic and xenograft tumor models with immunodeficiency of the specific (T- and B-cells) immune system. Because of this approach we focused on the cells of the innate immune system. Methods: Paraffin wax embedded primary breast cancers from the syngeneic mouse WAP-T model and from xenografted tumors of breast, colon, melanoma, ovarian, neuroblastoma, pancreatic, prostate and small cell lung cancer were investigated for the infiltration of immunocompetent cells. The percentage of the labelled cells was semiquantitatively recorded and attributed to the following locations: adjacent adipose tissue, the tumor capsule, the intra-tumoral septae and the malignant cells themselves. The following markers were used: CD45 as a pan-leukocyte marker, BSA-I as a marker for dendritic cells, CD11b as a marker for NK cells and CD68 for macrophages. Results: Xenograft tumors: in relation to the localisation of CD45, CD11b positive, NK and dendritic cells, the highest score was found in the adjacent adipose tissue, followed by lesser infiltration in the malignant tissue. The detected numbers of CD45 positive cells differed between the tumor entities: few infiltrating cells in breast, small cell lung cancer and in neuroblastoma, a moderate infiltration in colon cancer, melanoma and ovarian cancer and strongest in prostate and pancreatic cancer.Syngeneic tumors: the highest score of CD45, CD11b positive, NK and dendritic cells were observed in the tumor capsule, followed by a lesser degree of infiltration of the cancer tissue itself.Conclusions: Our findings show in several neoplastic entities that the majority of immune competent cells are not directly located at the malignant cells but are present in the surrounding tumor stroma and connective tissue capsule. Hence the tumor stroma represents a considerable barrier for lymphocytes to come in direct contact with the malignant cells. Therefore strategies should be employed to make the tumor stroma more penetrable for immune cells in order to increase their efficacy.

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Directing hypoxic tumor microenvironment and HIF to illuminate cancer immunotherapy's existing prospects and challenges in drug targets

Current Drug Targets ◽

10.2174/1389450123666220111114649 ◽

2022 ◽

Vol 23 ◽

Author(s):

Suman Kumar Ray ◽

Sukhes Mukherjee

Keyword(s):

Immune System ◽

Tumor Microenvironment ◽

Cancer Cells ◽

Drug Targets ◽

Therapeutic Potential ◽

Checkpoint Inhibitors ◽

Cancer Drug ◽

Cancer Therapies ◽

Cellular Expression ◽

Hypoxic Tumor

Abstract: Cancer is now also reflected as a disease of the tumor microenvironment, primarily supposed to be a decontrolled genetic and cellular expression disease. Over the past two decades, significant and rapid progress has been made in recognizing the dynamics of the tumor's microenvironment and its contribution to influencing the response to various anti-cancer therapies and drugs. Modulations in the tumor microenvironment and immune checkpoint blockade are interesting in cancer immunotherapy and drug targets. Simultaneously, the immunotherapeutic strategy can be done by modulating the immune regulatory pathway; however, the tumor microenvironment plays an essential role in suppressing the antitumor's immunity by its substantial heterogeneity. Hypoxia inducible factor (HIF) is a significant contributor to solid tumor heterogeneity and a key stressor in the tumor microenvironment to drive adaptations to prevent immune surveillance. Checkpoint inhibitors here halt the ability of cancer cells to stop the immune system from activating, and in turn, amplify your body's immune system to help destroy cancer cells. Common checkpoints that these inhibitors affect are the PD-1/PD-L1 and CTLA-4 pathways and important drugs involved are Ipilimumab and Nivolumab, mainly along with other drugs in this group. Targeting the hypoxic tumor microenvironment may provide a novel immunotherapy strategy, break down traditional cancer therapy resistance, and build the framework for personalized precision medicine and cancer drug targets. We hope that this knowledge can provide insight into the therapeutic potential of targeting Hypoxia and help to develop novel combination approaches of cancer drugs to increase the effectiveness of existing cancer therapies, including immunotherapy.

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Tissue-specific cancer stem cells: reality or a mirage?

Translational Medicine Reports ◽

10.4081/tmr.6535 ◽

2017 ◽

Vol 1 (1) ◽

Cited By ~ 4

Author(s):

Tarik Regad

Keyword(s):

Stem Cells ◽

Cancer Stem Cells ◽

Cancer Cells ◽

Cancer Patients ◽

Targeted Therapies ◽

Cancer Recurrence ◽

Cancer Therapies ◽

Malignant Cells ◽

Significant Progress ◽

Specific Cancer

Equo ne credite, Teucri. Quidquid id est, timeo Danaos et dona ferentes (Do not trust the horse, Trojans! Whatever it is, I fear the Greeks, even bringing gifts) said Laocoön (Virgil, the Aeneid book). Cancer stem cells (CSCs) are populations of cancer cells that can be found in different cancerous tissues and organs, and have properties that are similar to normal stem cells. They are thought to be chemo-resistant and radioresistant and are therefore responsible for cancer recurrence and relapse encountered in cancer patients following chemotherapy and radiotherapy. Although significant progress has been made to characterise CSCs, it is becoming clear that the failure of cancer therapies directed against certain types of aggressive cancers is due to the presence of these malignant cells. Cancer therapies that will rely on a combination of CSCs-targeted therapies, chemotherapy and radiotherapy are more likely to succeed in eradicating aggressive cancers and prevent recurrence in treated patients.

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Solasodine Rhamnosyl Glycosides Cause Apoptosis in Cancer Cells. Do They Also Prime the Immune System Resulting in Long-Term Protection against Cancer?

Planta Medica ◽

10.1055/s-0031-1298149 ◽

2012 ◽

Vol 78 (04) ◽

pp. 349-353 ◽

Cited By ~ 13

Author(s):

Bill Cham ◽

Tania Chase

Keyword(s):

Immune System ◽

Cancer Cells ◽

Apoptosis In Cancer Cells

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Extracellular Acidification Induces Lysosomal Dysregulation

Cells ◽

10.3390/cells10051188 ◽

2021 ◽

Vol 10 (5) ◽

pp. 1188

Author(s):

Bryce Ordway ◽

Robert J. Gillies ◽

Mehdi Damaghi

Keyword(s):

Cancer Cells ◽

Ductal Carcinoma ◽

Acid Stress ◽

Extracellular Acidification ◽

Evolutionary Selection ◽

Somatic Evolution ◽

Short Period ◽

Different Types ◽

Extracellular Environment

Many invasive cancers emerge through a years-long process of somatic evolution, characterized by an accumulation of heritable genetic and epigenetic changes and the emergence of increasingly aggressive clonal populations. In solid tumors, such as breast ductal carcinoma, the extracellular environment for cells within the nascent tumor is harsh and imposes different types of stress on cells, such as hypoxia, nutrient deprivation, and cytokine inflammation. Acidosis is a constant stressor of most cancer cells due to its production through fermentation of glucose to lactic acid in hypoxic or normoxic regions (Warburg effect). Over a short period of time, acid stress can have a profound effect on the function of lysosomes within the cells exposed to this environment, and after long term exposure, lysosomal function of the cancer cells can become completely dysregulated. Whether this dysregulation is due to an epigenetic change or evolutionary selection has yet to be determined, but understanding the mechanisms behind this dysregulation could identify therapeutic opportunities.

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Potential of Mesenchymal Stem Cells in Anti-Cancer Therapies

Current Stem Cell Research & Therapy ◽

10.2174/1574888x15666200310171547 ◽

2020 ◽

Vol 15 (6) ◽

pp. 482-491 ◽

Cited By ~ 1

Author(s):

Milena Kostadinova ◽

Milena Mourdjeva

Keyword(s):

Cancer Cells ◽

Small Population ◽

Tumor Formation ◽

Bioactive Molecules ◽

Cancer Therapies ◽

New Methods ◽

Cycle Arrest ◽

Anti Cancer ◽

Blocking Mechanisms

Mesenchymal stem/stromal cells (MSCs) are localized throughout the adult body as a small population in the stroma of the tissue concerned. In injury, tissue damage, or tumor formation, they are activated and leave their niche to migrate to the site of injury, where they release a plethora of growth factors, cytokines, and other bioactive molecules. With the accumulation of data about the interaction between MSCs and tumor cells, the dualistic role of MSCs remains unclear. However, a large number of studies have demonstrated the natural anti-tumor properties inherent in MSCs, so this is the basis for intensive research for new methods using MSCs as a tool to suppress cancer cell development. This review focuses specifically on advanced approaches in modifying MSCs to become a powerful, precision- targeted tool for killing cancer cells, but not normal healthy cells. Suppression of tumor growth by MSCs can be accomplished by inducing apoptosis or cell cycle arrest, suppressing tumor angiogenesis, or blocking mechanisms mediating metastasis. In addition, the chemosensitivity of cancer cells may be increased so that the dose of the chemotherapeutic agent used could be significantly reduced.

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Emerging roles of cancer-testis antigenes, semenogelin 1 and 2, in neoplastic cells

Cell Death Discovery ◽

10.1038/s41420-021-00482-4 ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Oleg Shuvalov ◽

Alyona Kizenko ◽

Alexey Petukhov ◽

Olga Fedorova ◽

Alexandra Daks ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Tumor Cells ◽

Reproductive System ◽

Seminal Fluid ◽

Cancer Development ◽

Migration And Invasion ◽

Malignant Cells ◽

Cancer Testis

AbstractCancer-testicular Antigens (CTAs) belong to a group of proteins that under normal conditions are strictly expressed in a male’s reproductive tissues. However, upon malignisation, they are frequently re-expressed in neoplastic tissues of various origin. A number of studies have shown that different CTAs affect growth, migration and invasion of tumor cells and favor cancer development and metastasis. Two members of the CTA group, Semenogelin 1 and 2 (SEMG1 and SEMG2, or SEMGs) represent the major component of human seminal fluid. They regulate the motility and capacitation of sperm. They are often re-expressed in different malignancies including breast cancer. However, there is almost no information about the functional properties of SEMGs in cancer cells. In this review, we highlight the role of SEMGs in the reproductive system and also summarize the data on their expression and functions in malignant cells of various origins.

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Life after Cell Death—Survival and Survivorship Following Chemotherapy

Cancers ◽

10.3390/cancers13122942 ◽

2021 ◽

Vol 13 (12) ◽

pp. 2942

Author(s):

Tamara Mc Erlain ◽

Aileen Burke ◽

Cristina M. Branco

Keyword(s):

Cancer Cells ◽

Surgical Excision ◽

Tumour Burden ◽

Physical Damage ◽

Term Care ◽

Treatment Practices ◽

Number Of Patients ◽

Cancer Types

To prevent cancer cells replacing and outnumbering their functional somatic counterparts, the most effective solution is their removal. Classical treatments rely on surgical excision, chemical or physical damage to the cancer cells by conventional interventions such as chemo- and radiotherapy, to eliminate or reduce tumour burden. Cancer treatment has in the last two decades seen the advent of increasingly sophisticated therapeutic regimens aimed at selectively targeting cancer cells whilst sparing the remaining cells from severe loss of viability or function. These include small molecule inhibitors, monoclonal antibodies and a myriad of compounds that affect metabolism, angiogenesis or immunotherapy. Our increased knowledge of specific cancer types, stratified diagnoses, genetic and molecular profiling, and more refined treatment practices have improved overall survival in a significant number of patients. Increased survival, however, has also increased the incidence of associated challenges of chemotherapy-induced morbidity, with some pathologies developing several years after termination of treatment. Long-term care of cancer survivors must therefore become a focus in itself, such that along with prolonging life expectancy, treatments allow for improved quality of life.

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