The link between cancer and our immune systems
Cancer cells are characterised by their uncontrollable growth, often called cell proliferation. The immune system has been found to respond to cancer cells in some instances, recognising the abnormally proliferating cells as foreign, or ‘non-self’. Studies have shown that some immune cells can be found in, and surrounding, cancer cells. These are known as tumour infiltrating cells (TIL). As a result, researchers have begun to develop ways in which we can boost a patient’s own immune system to help in cancer treatments and prevent the tumour from spreading to the rest of the body (metastasising). This is known as immunotherapy.
Despite the potential of immunotherapy in cancer treatment, it comes with a whole host of its own challenges. The link between cancer and the immune system was first recognised in the 19th century when Rudolf Virchow published his findings that cancers occurred in areas of inflammation. As of today, it is still widely accepted that inflammation is a key causative agent in cancer formation. Additionally, cancer cells have developed unique traits to help them evade the immune system, such as expression of proteins allowing them to go unrecognised by the immune system and the expression of proteins on their surface which act to down-regulate or inhibit immune activity.
So, how have we been taking back the power of our immune systems in the fight against cancer?
Immune checkpoints function to stop the immune system from over-acting, which could be potentially damaging to healthy cells. These checkpoints are triggered when T cells, an immune cell, interact with receptors on target cells which signal for a down-regulation of immune response. As shown in the image below, cancers can express these proteins, allowing them to down-regulate the immune response to them and evade the immune system. By creating drugs which block this interaction, it allows the immune response to react with full force against the cancer cells.
Figure 1: These checkpoint inhibitors stop the cancer from damponing the immune response and allow a stronger immune response to cancer cells. Sasidharan Nair, V. and Elkord, E. (2018) ‘Immune checkpoint inhibitors in cancer therapy: a focus on T‐regulatory cells’, Immunol Cell Biol, 96(1), pp. 21–33. doi: 10.1111/imcb.1003.
T-cell Transfer Therapy
So, what are T-cells? T-cells belong to a family of the immune cells called lymphocytes. T-cells exist in the body in small amounts, and when they interact with something they recognise as foreign, such as an infection, the body then produces more T-cells which are specific to fighting off that infection.
T-cell transfer therapy involves increasing the immune response to cancer by upregulating T-cell activity outside the body, as it can sometimes be hard for T-cells to distinguish cancer cells as diseased. This can be done via two methods, TIL (tumour infiltrating lymphocyte) therapy and CAR-T cell therapy.
Both methods involve taking a sample of the patients T-cells and multiplying (upregulating) them in the lab. CAR-T goes a step further, as the T-cells taken from the patient are then altered (genetically modified) to express something called ‘CAR’ (Chimeric antigen receptor). The addition of CAR to the T-cells allows them to target cancer cells more easily by recognition of surface proteins specific to them.
TIL therapy involves upregulation of the most effective lymphocyte around the tumour microenvironment. T-cells found in, and around, the tumour is known as tumour-infiltrating cells (TIL’s). In comparison to CAR T-cell therapy, it is assumed that T-cells found near the tumour can already effectively recognise and target cancer cells.
Cytokines are a type of immune system modulator (acting to increase immune response) and include cytokines such as interferons and interleukins. The interferon INF-α can be used to amplify the immune response by activating certain immune cells. Interleukins on the other hand are used specifically to increase white blood cell count, including T-lymphocytes previously mentioned. Cytokines can be given to patients in an injection or intravenously through a drip and unusually involves a repeat treatment depending on the cancer type.
These are only a few of the current methods, and there are still lots of exciting developments in immunotherapy. For a more in-depth exploration of the topic, visit the following webinar all about immunotherapy, the science behind it, it’s potential, and the patient perspective:
Garner, H. and de Visser, K. E. (2020) ‘Immune crosstalk in cancer progression and metastatic spread: a complex conversation’, Nat Rev Immunol, 20(8), pp. 483–497. doi: 10.1038/s41577-019-0271-z.
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Kumar, A., Swain, C. A. and Shevde, L. A. (2021) ‘Informing the new developments and future of cancer immunotherapy : Future of cancer immunotherapy’, Cancer Metastasis Rev.
Raskov, H. et al. (2021) ‘Cytotoxic CD8 + T cells in cancer and cancer immunotherapy’, Br J Cancer, 124(2), pp. 359–367. doi: 10.1038/s41416-020-01048-4.
Sasidharan Nair, V. and Elkord, E. (2018) ‘Immune checkpoint inhibitors in cancer therapy: a focus on T‐regulatory cells’, Immunol Cell Biol, 96(1), pp. 21–33. doi: 10.1111/imcb.1003.