The Intestinal Tumour Microenvironment

Cancer is one of the leading causes of death worldwide, and current research has focused on the discovery of novel approaches to effectively treat this disease. Recently, a considerable number of clinical trials have demonstrated the success of immunomodulatory therapies for the treatment of cancer. Monoclonal antibodies can target components of the immune system to either i) agonise co-stimulatory molecules, such as CD137, OX40 and CD40; or ii) inhibit immune checkpoints, such as cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), programmed cell death-1 (PD-1) and its corresponding ligand PD-L1. Although tumour regression is the outcome for some patients following immunotherapy, many patients still do not respond. Furthermore, chemotherapy has been the standard of care for most cancers, but the immunomodulatory capacity of these drugs has only recently been uncovered. The ability of chemotherapy to modulate the immune system through a variety of mechanisms, including immunogenic cell death (ICD), increased antigen presentation and depletion of regulatory immune cells, highlights the potential for synergism between conventional chemotherapy and novel immunotherapy. In addition, recent pre-clinical trials indicate dipeptidyl peptidase (DPP) enzyme inhibition, an enzyme that can regulate immune cell trafficking to the tumour microenvironment, as a novel cancer therapy. The present review focuses on the current immunological approaches for the treatment of cancer, and summarizes clinical trials in the field of immunotherapy as a single treatment and in combination with chemotherapy.

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The Mechanism of Lunasin's Effect on the Growth of Breast Cancer Cells Induced by Obesity-induced Inflammation

Impact ◽

10.21820/23987073.2020.7.16 ◽

2020 ◽

Vol 2020 (7) ◽

pp. 16-18

Author(s):

Chia-Chien Hsieh

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Inflammatory Responses ◽

Specific Area ◽

Tumour Microenvironment ◽

Associate Professor ◽

World Health ◽

Cancer Development ◽

Breast Cancer Development

It has long been established that diet and nutrition can have a significant impact on health and even help reduce the prevalence of chronic diseases. It makes sense that what we put into our bodies would have some bearing on how our bodies function. Indeed, the World Health Organization developed guidelines focusing on nutrient intake, with a view to reducing the global burden of disease related to obesity, diabetes, cardiovascular disease, several forms of cancer, osteoporosis and dental disease. One exciting area of research, that is little understood, is the potential efficacy of lunasin – a peptide found in soy, legume and some cereal grains – against certain types of cancer. Lunasin has shown potential in the prevention of cancers. It is able to do this by suppressing the proliferation and migration of cancer cells, and anti-inflammation in this tumour environment. A specific area of study within this is lunasin's ability to reduce obesity associated breast cancer development. Associate Professor Chia-Chien Hsieh, a researcher based at the Programs of Nutrition Science, School of Life Science, National Taiwan Normal University, current work is focused on the mechanism of lunasin's effect on the growth of breast cancer cells induced by obesity-associated inflammation. Her goal is to investigate the obesity-related breast cancer chemoprevention of lunasin, which might retard inflammatory responses around tumour microenvironment and even break the crosstalk of macrophages, adipocyte, and breast cancer cells. The aim being to provide potential strategies for ameliorating obesity-related ER(+) or ER(-) breast cancer development.

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The roles of TGFβ in the tumour microenvironment

Nature Reviews Cancer ◽

10.1038/nrc3603 ◽

2013 ◽

Vol 13 (11) ◽

pp. 788-799 ◽

Cited By ~ 498

Author(s):

Michael Pickup ◽

Sergey Novitskiy ◽

Harold L. Moses

Keyword(s):

Tumour Microenvironment

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Targeting obesity-related dysfunction in hormonally driven cancers

British Journal of Cancer ◽

10.1038/s41416-021-01393-y ◽

2021 ◽

Author(s):

Maria M. Rubinstein ◽

Kristy A. Brown ◽

Neil M. Iyengar

Keyword(s):

Cell Signalling ◽

Treatment Resistance ◽

Tumour Microenvironment ◽

Subsequent Increase ◽

Treatment And Prevention ◽

Cancer Pathogenesis ◽

Diet And Exercise ◽

Systemic Factors ◽

Tumour Vascularity ◽

Obesity And Cancer

AbstractObesity is a risk factor for at least 13 different types of cancer, many of which are hormonally driven, and is associated with increased cancer incidence and morbidity. Adult obesity rates are steadily increasing and a subsequent increase in cancer burden is anticipated. Obesity-related dysfunction can contribute to cancer pathogenesis and treatment resistance through various mechanisms, including those mediated by insulin, leptin, adipokine, and aromatase signalling pathways, particularly in women. Furthermore, adiposity-related changes can influence tumour vascularity and inflammation in the tumour microenvironment, which can support tumour development and growth. Trials investigating non-pharmacological approaches to target the mechanisms driving obesity-mediated cancer pathogenesis are emerging and are necessary to better appreciate the interplay between malignancy, adiposity, diet and exercise. Diet, exercise and bariatric surgery are potential strategies to reverse the cancer-promoting effects of obesity; trials of these interventions should be conducted in a scientifically rigorous manner with dose escalation and appropriate selection of tumour phenotypes and have cancer-related clinical and mechanistic endpoints. We are only beginning to understand the mechanisms by which obesity effects cell signalling and systemic factors that contribute to oncogenesis. As the rates of obesity and cancer increase, we must promote the development of non-pharmacological lifestyle trials for the treatment and prevention of malignancy.

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