The immune system and cancer

The immune system protects organisms against foreign pathogens such as bacteria, viruses and fungi as well as an organism’s own cancerous cells.

The immune system is complex and is made up of different organs, cells, and proteins.

The two major subsystems of the human immune system are the innate and adaptive immune systems.

The innate immune system
The innate immune system provides a first immediate response to pathogens.  The innate immune system detects so-called PAMPs (Pathogen Associated Molecular Patterns) which are larger structures that do not normally occur in human bodies. Examples include microbial cell-walls and viral RNA molecules. Upon their detection, the innate immune system activates cells to attack and destroy the outsider while also informing the adaptive immune response. Important cells in the innate immune system include so-called macrophages, neutrophils, dendritic cells, mast cells and basophils as well as natural killer cells. The innate immune system can develop persistent resistance to reinfection, a phenomenon termed trained immunity or innate immune memory.

The adaptive immune system
The adaptive immune system provides a second and tailored response to each stimulus by learning to recognise molecules it has previously encountered. The cells of adaptive immunity include B-cells and T-cells. Both target viruses and/or bacteria on the basis of molecules that differ from those of the host. After the first response, B- and T-cells that recognised the foreign molecule remain as memory cells and provide a faster and stronger response should the pathogen return. This memory is also the basis for vaccination; the adaptive immune system will quickly recognise a molecule to which it responded previously. As a result, the adaptive immune system can efficiently & quickly target any recurring infection.

Regulation of the immune system
The immune system targets pathogens but should not attack healthy cells. The immune system therefore comprises all kinds of checks and balances designed to prevent the immune system from killing an organism’s non-pathogenic cells. Since these cells include desirable bacteria (such as the gut and skin microbiome) as well as an organism’s own cells, these checks and balances are very important. Auto-immune diseases can happen if an organism’s immune-system mistakenly does target healthy cells and can be severe and difficult to treat.

The immune system develops in such a manner that it distinguishes foreign molecules from molecules that naturally occur on healthy cells. As a result, the immune system is designed to only use molecules that are unique to a pathogen. In addition, healthy cells express so-called immune checkpoints that further suppress a possible undesired auto-immune response.   

The immune system & cancer
Cancers can develop in cells of the immune system; multiple kinds of leukaemia & lymphoma are cancers of the immune system itself. 

Otherwise, the immune system is an essential safeguard against cancer. The immune system is known to kill cancerous and pre-cancerous cells and will often prevent cancer growth.

The immune system can specifically target cancer cells since they are genetically and hence phenotypically different and can present new proteins, polysaccharides, lipids and combinations thereof on their cell surface that can be recognised by the immune system.

Natural killer cells, dendritic cells , polymorphonuclear neutrophils, and macrophages are first-line effectors to damaged cells and cancer cells. Natural killer T cells and γδ T cells play roles as both innate and adaptive components, through close interactions with cells of the adaptive immune system.

Not all cancer cells are eliminated by the immune system: tumours that proliferate either do not express sufficient cancer specific molecules to trigger an immune response or (over)express immune checkpoints.

As sketched above, cancers continue to evolve and evasion of the immune response is a hallmark of tumours. If therefore an initial immune response against a cancer specific molecule is successful, the evolutionary pressure that the cancer cells are under can result in cells on which the molecule is no longer expressed and that the immune system therefore no longer targets and/or in cells that prevent an immune response by expressing immune checkpoints. Ideally therefore, the immune system is able to adapt to such cancer evolution.