Will We Find a Cure for Cancer?: A Medical Biology Digest on Immunotherapy, Key Questions And Ideas To Explore
Suitable for students with a broad range of interests, this medical-biology digest explores promising new ideas in cancer treatment that have emerged in recent years, with a focus on the exciting prospects for immunotherapy in cancer treatment. Through inclusion of a range of thinking tasks and ideas for further exploration, particularly useful for those with prospective university interviews, the digest aims to encourage students to develop originality of thought and informed opinions about scientific news articles which will guide further interest in particular fields and interesting research questions.
Question 1: Will we find a cure for cancer?
To answer this question, first get to grips with the terminology - what is cancer? Research current prevention: screening and vaccination, and the different cancer treatments available. Our article on combatting cancer: https://www.mindsunderground.com/muarticles/can-cancer-be-combatted, will introduce you to what cancer is, the hallmarks of cancer, and cancer therapies that target a range of these hallmarks.
Question 2: Tell me about an interesting article or research paper you've read about cancer
For those aspiring to university/ a future career in a STEM subject, it is important to engage beyond the classroom by reading books and scientific articles on topics of interest. Also be prepared to talk about what you read and form opinions / criticisms.
Key Steps:
(i) Ensure you have clearly read and understood the article;
Try to rationalise the data, and understand the complex stats which govern scientific research
Be aware of and careful of the language you use when explaining phenomena - avoid overly committed language like 'will' and 'is' when talking about unknowns - instead use less committed language like 'may' or 'could'. This is important due to the nature of uncertainty in medicine and science
(ii) Ensure you critically appraise the article;
The exercise of critical appraisal is centred around ensuring that you’ve understood a complex topic and are able to articulate a response in your own words whilst also critiquing the article. This makes for a far more concise and coherent response
Our previous MU Medicine Edition provides tips on reading research papers and critical appraisal: Curious Minds: Medicine Edition
(iii) Try to pre-empt different lines of questioning and giving a response
Journal Article Link (click the image or access the article here: https://bmcmedicine.biomedcentral.com/track/pdf/10.1186/s12916-016-0623-5.pdf)
The Prospects For Immunotherapy in Cancer Treatment
MU Mastermind, Síle, has written a Medical Biology lay article on Immunotherapy as a key emerging cancer treatment to research in more detail below. Síle has a BSci, MRes and PhD in biologically sciences, and is a graduate medical student at Oxford University. She has extensive experience in aiding students to explore beyond the syllabus in the contexts of both science and medicine).
Cancer immunotherapy is a therapeutic strategy which harnesses the tumour-killing ability of the immune system against cancer. This therapeutic approach has gained momentum in the last decade, and some of the results are incredibly promising. The immune system is highly complex, which is perhaps why it has taken so long for cancer researchers to fully understand how to manipulate it for the purposes of therapy. It is made up of multiple cell types whose primary goal is to protect us from ‘foreign’ matter. This ‘foreign’ matter includes bacteria, viruses and also tumours.
How does the immune system launch an immune response?
There are many components involved in launching an immune response against foreign matter. The eradication of a foreign body is broadly a two-step process: recognition and elimination. Recognition is carried out by cells known as macrophages or dendritic cells who can sense the presence of foreign matter by molecules present on its surface, which the immune cells recognise as being different to the body’s own. The macrophages or dendritic cells can then engulf the foreign matter, transfer the molecules to its own surface, where they can be read by T cells. T cells play a very important role in immune defense as they can mediate cell death of cells they know to be foreign as directed by macrophages and dendritic cells.
What does the immune response do to cancer?
In the case of cancer, the immune system often plays an important role in removing developing tumours. It is believed that throughout our lifetime, many tumours are detected and removed by the immune system without us even knowing it. Tumours are deemed ‘foreign’ by the immune system because they often contain molecules on their surface which are different from the rest of the cells in the body.
However, some tumours are more tactical than others. Some tumour cells can acquire the ability to silence the immune cells and can convert them ‘to the dark side’ where they actually help the tumours to grow! One cell type which is duped by cancer cell is the macrophage. Tumour cells can produce signals for macrophages which turn ‘on’ the growth programme in the macrophage, turning ‘off’ the tumour- cell-engulfing immune function. This means that when the T cells pay a visit, the macrophages don’t inform them that there is foreign matter in their midst, an immune response is not induced and the tumour continues to grow.
Furthermore, the tumour cells can transport molecules to their cell surface to engage and directly silence T cell activity. T cells, like most cells, have molecules on their cell surface called receptors. These receptors can bind to specific ‘ligands’ on other cells which can induce an action, or in this case, an inaction. T cells express a receptor called programmed death-1 (PD-1). The purpose of this receptor is to inhibit immune cells following an inflammatory cascade, as excess immune activity can unnecessarily damage tissue. Many tumour cells conveniently display the ligand for PD-1 (PD-L1) on their cell surface. Therefore, when a T cell does come ‘round for a visit’, the tumour cell interacts with the T cell via the PD-1/PD-L1 interaction. When this happens, the T cell is virtually immobilised and can’t kill the tumour cells. The T cell is inhibited from proliferating and from releasing molecules to attract other T cells. As it is the T cell which is deemed to be the key player in taking down a tumour, they have been the focus of much cancer immunotherapy research.
T cells breaking free
A strategy, which has proved highly successful in clinical trials, is the breaking up of the inhibitory interactions between tumour cells and T cells, such as the PD-1/PD-L1 axis outlined above. The PD-1/PD-L1 interaction is clinically relevant as the presence of PD-1 on tumour cells directly correlates with poor prognosis in multiple cancer types such as breast, kidney, gastric, pancreatic and bladder cancers. One such agent, pembrolizumab, binds to PD-1, and when administered to patients with metastatic melanoma, 78% experienced tumour regression.
Another interaction targeted by therapeutic intervention is the cytotoxic T lymphocyte antigen 4 (CTLA-4). CTLA-4, like PD-1, can be present on the surface of cancer cells and prevents T cells from killing tumours. A drug called ipilimumab (the names are getting worse) was approved by the Food and Drug Administration in 2011 after it was seen to significantly increase the survival rates of metastatic melanoma patients treated with the CTLA-4 agent plus standard therapy compared to patients treated with the standard agent alone.
Taking out the T cells and putting them back in again
Another therapeutic option known as ‘Adoptive T Cell Transfer’. This neat technique involves the removal of T cells from a cancer patient’s own blood. The T cells which are competent at killing tumour cells can be isolated in the laboratory and grown in number up to billions. These cells can then be injected back into the cancer patient from where they came to kill the patient’s cancer. Such a technique has had quite impressive results. An important clinical trial, carried out by the ‘father of adoptive T cell transfer,’ Rosenberg, found that in 93 patients with metastatic melanoma who underwent the procedure, 56% achieved a positive clinical response. Furthermore, 95% of these responses were ongoing in subsequent years following the treatment. This therapeutic platform has progressed to genetic engineering of the isolate T cells to make them even more potent at killing tumour cells. This can be achieved by taking T cells from the patients as above and engineering them to display any anti-cancer molecules the researcher wants. One of the greatest winners of this technology is blood cancers. One study saw 75% of patients suffering from either B- cell lymphoma or chronic lymphocytic leukemia experience a positive response.
Future prospects for cancer immunotherapy
These are just some of many cancer immunotherapies which are making their way to clinic. However, the cancer immunotherapy story is not without its limitations: many of the immune interventions can lead to autoimmune-like side effects such as inflammation of the gut and joint. However, given the toxicities of other cancer therapies such as chemotherapy, immunotherapy is still regarded as highly promising and reasonably tolerable for cancer patients.
What is particularly eloquent about the immune approach to cancer treatment is that like elephants, the immune system does not forget. This means that if a person experiences the same tumour a second time, the immune system will have already built up a defense against it, and can deal with it swiftly. However, this does not prevent the cancer from further evolving beyond the immune interventions we treat with. This mechanism, as well as mechanisms to control the autoimmune side effects, is high priority for young PhD researchers across the world, and understanding these could solidify cancer immunotherapy as the prevailing cancer treatment in the future.
Further Questions on Cancer:
What goes wrong for cancers to develop? (This was one of the questions for the 2021 Minds Underground Medicine Essay Competition!)
What are the pros and cons of implementing a population screening programme for cancers or other illnesses?
What do you think is most promising in the future of medicine?
Cancer immunotherapies were named Science’s Breakthrough of the Year in 2013.
Did they warrant this title given their demonstration of durable responses in only a subset of patients?
How have cancer immunotherapies progressed in the last decade?
How will they continue to progress in the future?
Further Reading & Research
Nature Journal provide a run-through of key research articles on Immunotherapy
Siddhartha Mukherjee’s seminal text, The Emperor of All Maladies is a must-read
Tumour immunology and immunotherapy video by Nature: https://www.youtube.com/watch?v=K09xzIQ8zsg
Science. 20 Dec 2013 DOI:10.1126/science.342.6165.1432 Cancer Immunotherapy Jennifer Couzin Frankel
Cell Press. Jun 2013 DOI: 10.1016/j.immuni.2013.07.012 Oncology Meets Immunology: The Cancer Immunity Cycle Daniel S. Chen and Ira Mellman
(Advanced) Cancer Discovery 2018 DOI: 10.1158/2159-8290.CD-18-0367: Fundamental Mechanisms of Immune Checkpoint Blockade Therapy, Spencer C. Wei, Colm R. Duffy and James P. Allison
N Engl J Med. 2018 Jul DOI: 10.1056/NEJMra1706169. Chimeric Antigen Receptor Therapy June CH, Sardelain M
(Advanced) Cancer Discovery 2018 DOI: 10.1158/2159-8290.CD-18-0297 CARs versus BiTEs: A Comparison between T Cell–Redirection Strategies for Cancer Treatment Clare Y. Slaney, Pin Wang, Phillip K. Darcy and Michael H. Kershaw
Learn More About Cancer Research & Other Cutting-Edge Topics From Our Oxbridge Subject Specialists
Our Medicine Summer School for medical applicants runs 27th June - 12th Sept (Sundays 5.30-6.30pm), with 12 exciting interactive classes on topics such as “Can we find a cure for cancer?”. View the full PDF course outline & host bios here
The Biology/ Biological Natural Sciences Summer School runs 22nd June - 7th Sept (Tuesdays 5.30-6.30pm). View the full PDF course outline & host bios here
The Veterinary Summer School runs 27th June - 12th Sept (Sundays 5.30-6.30pm). View the full PDF course outline & host bios here
Our Work/ Research Experience Projects combine teaching of high-level subject-specific content with exposure to real-world applications of these concepts, giving you the opportunity to undertake a project that is both useful for a university application and future career. Check out our latest cancer project outline here.