The increase in human life expectancy over millenia has been mainly as a result of our immune system’s ability to fight microbial infection: we rely on its rapidity, precision, adaptation and efficiency. All of these features are ideal for the immune system to target cancer in a similarly lethal way. The evolution of knowledge in how the immune system works encompasses amongst the greatest scientific minds and has been littered with Nobel prize awards along the way. From early success such as antibody therapy and immune molecules such as interferon and interleukin-2, we have made gigantic leaps forward over 15 years such that we are now considering immunotherapy as the first option for a number of cancers- ahead of conventional cancer treatments. While individual drugs may have made the headlines, this success is due to sustained investment in the science and our understanding how the immune system works in health, and how this is subverted in countless ways in cancer.
In all cancers, even tiny early cancers, the immune system detects the cancer and sends in immune cells to try and combat. In time, as the cancer grows, this immune response is subdued and, ultimately, suppressed completely. Cancers then form complex ecosystems, comprising cancer cells, normal structural cells, blood vessels, ‘good’ and ‘bad’ immune cells in a conformation that has texture or ‘sponginess’, regions of differing oxygenation and variable tissue density. This ecosystem favours and sustains the cancer.
New immunotherapies are therefore trying to target cancers cells and components of this ecosystem. We now also know that most cancers are colonised with bacteria, and the type of bacteria inside cancer cells may help damage the cancer or allow it to flourish. Altering the resident bacteria in cancers will form part of future treatments.
Immunotherapy treatments of cancer are not direct assaults on tumours but more indirect, by stimulating production of immune cells (T cells, B cells, natural killer cells), which then traffic to the tumour, and try and cause damage of the cancer cells specifically. However, this has proved insufficient as a treatment: the great progress has been how to enhance these immune cells further by removing the ‘brakes’ the body normally applies (to stop immune cells becoming overactive). As a result, and 2 more Nobel prizes later, we have 2 immunotherapies, ipilimumab and nivolumab, which allows over half the patients with aggressive melanoma to survive 10 years, versus the dismal 6-9 months we expected previously.
These drugs were the spark- we are now in times of incredible technical analytical sophistication and generation of supercharged immune cells as the next generation of treatments. What is changing quickly further is the need for a broader or ‘systems’ approach- we know we have to change the physical structure of the ecosystem (or ‘tumour microenvironment’) the cancers have evolved to protect itself (i.e. damage it with drugs, cancer killing viruses or radiation) and combine this with immune attack.
These are exciting times: engineered T cells, dendritic cell, cancer vaccines, the next generation of antibodies (called bi-specifics) are a few examples of what’s is heading rapidly to the clinic, and for cancers where immune manipulation was thought never to be possible such as lung cancer and prostate cancer.
It would be great if you could engage with Cancer Immunotherapy Month. You can donate to Topic of Cancer using our page on Virgin moneygiving page, or perhaps, you could raise money for our research team. Every little helps, and is greatly appreciated.
You can read more about immunotherapy on our website by clicking here.
Topic of Cancer is a registered charity in England and Wales, registered no. 1151079.
Sir Paul Beresford MP | Michael Buerk | Michael Elwyn | Yvonne Hall | Martin O'Donnell | Glyn Powell-Evans | Colin Roy | Alison Steadman OBE
Kim Ronaldson (Chair) | Anne Powell-Evans (Vice-Chair) | Nigel Lewis-Baker MBE (Honorary Life President) | Sarah Bishop | Tony Chant | Alan Loryman (Treasurer) | Prof. Hardev Pandha | Abbie Sell