Abstract
Colorectal cancer (CRC) is one of the most frequent and deadly forms of cancer. About half of patients are affected by metastasis, with the cancer spreading to e.g., liver, lungs or the peritoneum. The majority of these patients cannot be cured despite steady advances in treatment options. Immunotherapies are currently not widely applicable for this disease, yet show potential in preclinical models and clinical translation. The tumour microenvironment (TME) has emerged as a key factor in CRC metastasis, including by means of immune evasion—forming a major barrier to effective immuno-oncology. Several approaches are in development that aim to overcome the immunosuppressive environment and boost anti-tumour immunity. Among them are vaccination strategies, cellular transplantation therapies, and targeted treatments. Given the complexity of the system, we argue for rational design of combinatorial therapies and consider the implications of precision medicine in this context.
Highlights
The intestine is a vital organ for food digestion and has an important barrier function
In parallel with transcriptomic studies that were mostly focused on epithelial cancer cells, an additional paradigm emerged in understanding disease progression: a complicit tumour microenvironment (TME), or tumour stroma
This response aids the maturation of antigen presenting cells (APCs) such as dendritic cells (DCs), as well as their ability to present tumour-associated antigens (TAAs) to T cells [83]
Summary
The intestine is a vital organ for food digestion and has an important barrier function. This comes with an intricately balanced immune system that acts against pathogens, while tolerating beneficial microbiota as well as the foreign molecule antigens present in our food. Immune cells can detect and eliminate transformed cells to prevent the development of tumours, a process that is called immunosurveillance [1,2]. Successful cancers escape this mechanism in ways that are poorly understood [3].
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