What is Immunotherapy and how it can help your immune system to fight Cancer back?
As mentioned in previous blog posts, the main therapies for Cancer have been Chemotherapy, Surgery and Radiotherapy (See “What are the conventional Cancer therapies”). However, Immunotherapy has recently gained attention, after yielding promising results for as a Cancer therapy.
Immunotherapy is a type of Cancer therapy, that helps your immune system to fight back [1]. As mentioned in “Why does Cancer appear?”, immune system plays a crucial role in killing Cancer cells before they become tumors and it is the failure of immune system to fight the Cancer cells that ultimately leads to the formation of tumour and metastases [2]. Immunotherapy tries to reverse this process of failure of immune system and stimulate it to fight back. There are different Immunotherapies that are currently used to treat Cancer. Some of the main ones include Immune Checkpoint Inhibitors, CAR T cells and Cancer Vaccines.
Immune Checkpoint Inhibitors (ICIs) are monoclonal antibodies (immune system defence proteins made in a lab) that target special immune checkpoint proteins. These proteins act as “off-switches” in the immune cells [3], to prevent them from overreacting and damaging healthy tissues [4]. However, Cancer cells exploit these proteins by exhibiting them and deactivating the immune cells upon contact. This blocks the immune response and makes the immune system unable to fight Cancer. [3] The ICIs, in turn, block these proteins and thus prevents Cancer cells from inhibiting the immune cells. This ultimately leads to immune system fighting back and killing Cancer cells. [5]. They are also able to induce long term responses for some of the patients, prolonging their survival for many years. [6]. However, blocking the “brakes” of the immune system means that the immune cells will not be stopped even if they start attacking the healthy tissues, meaning the ICIs also lead to a series of immune related side effects. While most of them are mild and treated with corticosteroid drugs, they can rarely be severe. [7] Additionally, the efficacy of ICIs depends on a lot of different factors, such as the expression of those inhibitor proteins on Cancer cells (the lower the expression, the less effect ICI will yield, as if the Cancer cells do not use these checkpoints to avoid immune system, ICIs will not make big of a change), that are prevalent only in some tumours, making the therapy only effective to some. [5] ICIs are already used to treat melanoma (skin Cancer), lung, kidney and bladder Cancers. [8]
Chimeric Antigen Receptor T cells (CAR T cells) are revolutionary pillar of immunotherapy, that can produce remarkable clinical responses in patients. T cells are immune cells, which are extracted from patients body and genetically engineered to produce chimeric antigen receptors, that help them recognise certain proteins on the Cancer cells.[8] Almost every cell in the body have special complexes (called Major Histocompatibility Complex) on their membranes, that work as a “window” into the cell, showing what proteins are being made inside the cell. Some subtypes of T cells use these “windows” to see whether a cell makes abnormal proteins (like the Cancer cells do) and based on this they decide whether to kill the cell or not. However, Cancer cells can down regulate the number of these complexes they have, thus hiding from the immune cells. [9] This is a part of the issue CAR T cells are made to battle, because the Cancer cells will still have some proteins that will be targeted, as the CAR T cells bind to the target proteins that are independent of those complexes. This results in the reactivation of immune response and thus killing of the Cancer cell. However, CAR T cells also have major issues that include severe toxicities, resistance in the long term and the damage to healthy tissues that might have same proteins on their surface [10], which can also lead to a depletion in a type of immune cells called B cells [11], that are responsible for fighting off infections and immunity to previously encountered diseases. The CAR T cells are currently used to treat mainly liquid tumours, including blood and lymph Cancers. [8]
Cancer Vaccines can be either therapeutic (for treatment) or preventative. Therapeutic vaccines are designed for people who already have Cancer. They usually contain the proteins, that are associated with tumours (they are not present or are rare in normal cells). The idea behind this vaccine is the same as for every other vaccine. The immune cells should develop immunity towards these proteins (meaning the cells, that are ready to target those proteins when encountered will be made) which produces anti-Cancer response. [12] The Cancer treatment vaccines are used to treat bladder and prostate Cancers. Preventative vaccines work by targeting viruses, that increase the chances of an infected person to get Cancer. These include human papilloma virus (HPV) or hepatitis B. Even though it technically does not target Cancer cells, it does lower the risks of a person of developing Cancer. [13]
These are not the only immunotherapies that are being discovered, however. Others include using special viruses, that target tumours or using special immune system signalling proteins to induce inflammation at certain points. The main takeaway from this is that the field of immunotherapy is growing at an exciting rate and it does show promising results for some patients. And maybe in the near future, it will become the fourth pillar of the conventional medicine.
References:
National Cancer Institute. Immunotherapy for Cancer - National Cancer Institute [Internet]. www.cancer.gov. 2015. Available from: https://www.cancer.gov/about-cancer/treatment/types/immunotherapy#how-does-immunotherapy-work-against-cancer
Yang L, Ning Q, Tang S. Recent Advances and Next Breakthrough in Immunotherapy for Cancer Treatment. Cui D, editor. Journal of Immunology Research. 2022 Mar 18;2022:1–9.
Han Y, Liu D, Li L. PD-1/PD-L1 pathway: current researches in cancer. American Journal of Cancer Research [Internet]. 2020 Mar;10(3):727. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC7136921/#sec2
What are Immune Checkpoints, and How Can We Block Them? [Internet]. Hopkinsmedicine.org. 2016 [cited 2025 Feb 2]. Available from: https://www.hopkinsmedicine.org/news/articles/2016/01/what-are-immune-checkpoints-and-how-can-we-block-them
Shiravand Y, Khodadadi F, Kashani SMA, Hosseini-Fard SR, Hosseini S, Sadeghirad H, et al. Immune Checkpoint Inhibitors in Cancer Therapy. Current Oncology (Toronto, Ont). 2022 Apr 24;29(5):3044–60.
Rohit Thummalapalli, Ricciuti B, Chaitanya Bandlamudi, Muldoon D, Rizvi H, Elkrief A, et al. Clinical and Molecular Features of Long-term Response to Immune Checkpoint Inhibitors in Patients with Advanced Non–Small Cell Lung Cancer. Clinical Cancer Research [Internet]. 2023 Jul 11;29(21):4408–18. Available from: https://aacrjournals.org/clincancerres/article/29/21/4408/729643/Clinical-and-Molecular-Features-of-Long-term
Yin Q, Wu L, Han L, Xiao Z, Tong R, Lian L, et al. Immune-related adverse events of immune checkpoint inhibitors: a review. Frontiers in Immunology [Internet]. 2023 May 25;14. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10247998/#:~:text=The%20main%20gastrointestinal%20adverse%20reactions
National Cancer Institute. CAR T cells: Engineering immune cells to treat cancer [Internet]. National Cancer Institute. Cancer.gov; 2022. Available from: https://www.cancer.gov/about-cancer/treatment/research/car-t-cells
Cornel AM, Mimpen IL, Nierkens S. MHC Class I Downregulation in Cancer: Underlying Mechanisms and Potential Targets for Cancer Immunotherapy. Cancers [Internet]. 2020 Jul 2;12(7):1760. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7409324/
Sterner RC, Sterner RM. CAR-T Cell therapy: Current Limitations and Potential Strategies. Blood Cancer Journal. 2021 Apr 6;11(4):1–11.
Tur C, Eckstein M, Velden J, Rauber S, Bergmann C, Auth J, et al. CD19-CAR T-cell therapy induces deep tissue depletion of B cells. Annals of the Rheumatic Diseases [Internet]. 2024 Aug 17 [cited 2024 Sep 20];ard-2024-226142. Available from: https://ard.bmj.com/content/annrheumdis/early/2024/09/11/ard-2024-226142.full.pdf
