Once upon a time there was an organism, a pretty healthy, perfectly functioning organism. Sharing the same genetic material in a form of DNA inside, the cells of this organism were properly differentiated and performing their functions as well as they could.
However, the organism has been exposed to a large variety of factors, sometimes beneficial, sometimes detrimental to itself, to its DNA, such as smoking, physical activity, UV radiation, organic vegetables for dinner and hamburgers during the hectic days at stressful work. Moreover, every day the organism got older than the day before – inevitable aging. All those factors have contributed to some tiny changes in the DNA. We call them mutations.
Our body is well prepared for dealing with mutations: a great number of DNA-repair mechanisms work intensively all the time in every single cell of our body, to protect us from potentially harmful impact of mutations. Sometimes it is not enough though, partially due to our own lifestyle imperfections. We all have a certain threshold, different for everybody, a thin red line, after which our cell no longer functions normally; it goes out of control. Due to genetic and/or epigenetic mutations, a so-far regular cell of our body becomes a cancer cell and starts to divide uncontrollably and limitlessly. In short, this is how we develop a tumour.
Bladder cancer remains one of those cancer types with the highest amount of somatic mutations, and a relatively low amount of research. For over 30 years no new drugs have been developed, up to the immunotherapy era. It turns out that some bladder cancer patients respond quite well to the newly discovered immunotherapies, and if they do, the response is long-lasting, with relatively low side-effects of treatment. But do not be overhyped: only less than 30% of patients actually respond to this type of therapy.
Why only a small fraction of patients responds to immunotherapy? If they do, the response is rather durable. Why? This might relate to the immune system functioning on its own, or maybe with the entire organism, or maybe with some other environmental factors, which still remain undetected. Moreover, why do some patients develop auto-aggressive conditions, or in some rare cases, even hyperprogression of cancer upon immunotherapy administration?
In fact, the pace of research and clinical studies on cancer immunotherapy seems to outride the progress in understanding the underlying biological background. My research is focused on the crosstalk between a cancer cell and an immune system cell, for example a T cell. One of the most important abilities of our immune system is its ability to recognise cells as “foreign” or “own” – since cancer cells arise from our own body, it makes the process more difficult. Inside a small “gap” between a cancer cell and an immune system cell, called immunological synapse, there are checkpoint molecules. Those are small proteins at the cell’s membrane that need to be activated or deactivated in order to trigger immune response (or to inhibit the immune system from attacking). Even though necessary for proper functioning of our immune system, checkpoint molecules, in some situations, might help the disease to progress, as it takes place in several cancers escaping from immunity recognition and attack.
We still do not understand why T cells sometimes eliminate cancer cells, while other times they remain rather passive. Maybe cancer cells have more powerful weapons: maybe they use more sophisticated systems than solely checkpoint gene expression, like miRNAs? That is still to be discovered. The more we understand the functioning of this crosstalk, the more chances we get to target exactly the right point of the complex pathway and all our cells have a chance to live happily ever after.
About the Author
Paula Dobosz: Genetics – a discipline persecuted and disapproved by some, while being a source of fascination and hope for others. The rough way of life took me from a provincial town to the aged Cracow, where every day was full of new challenges. First, boring botany, then more and more joy, and eventually, PCRs every day. My path was not straight, but my scientific dreams were clearly oriented: cancer research. In all its shades and aspects. I studied Genetics, Psychology, Physical Education and Medicine; in Cracow, Warsaw and Cambridge. Finally, my path has lead me to Israel, where I am now as a post-doc. My research combines immunooncology and genetics; never a dull moment. Even though for me being a scientist is a demanding lifestyle rather than a profession itself, I always have time for myself. I am constantly in love with backpacker’s style of travelling, mountaineering, dancing and preserving old handcraft abilities.