FightCancer: Coming across the immune system – an early stage researcher (ESR7) from the CAPSTONE project explains

What does immunotherapy mean?
The word “immunotherapy” refers to every type of antitumour treatment enabling or boosting our immune system to fight cancer. In the last decade, the advent of immunotherapy has completely revolutionized the field of oncology by showing promising results in cancer therapies. However, the lack of successful responses in some patients sheds light on the urgent clinical need to better elucidate the biological mechanisms linked to the efficacy or failure of immunotherapy approaches.

What tools our immune system has to recognize cancer cells?
Immune cells play a crucial role in fighting cancer. Among these, T cells are the major drivers of anticancer immunity since they can recognize cancer cells and kill them. Cancer cells express specific molecules on their surface that are not expressed by healthy cells. These molecules mark the cancer cells as outsiders enabling T cells to recognise them as “danger”. The recognition of cancer cells by T cells is fundamental in establishing antitumour responses. Our body regulates this mechanism to prevent healthy cells from being attacked and destroyed by our immune system.

What are the mechanisms involved in cancer cell killing?
T cells are not killers by default. They can however become killers when required. Acquiring a killer instinct in T cells involves Dendritic cells, another class of immune cells with an essential role in antitumour immune responses. When cancer develops and progresses in our body, these cells reach out to the tumour site and catch fragments of cancer cells that diffuse in the tissue (fig. 1A). Upon the capture of these cancer cellularfragments, Dendritic cells activate a complex mechanism to express extracts of these cancer fragments at their surface (fig. 1B). This mechanism is still under investigation and yet to be explained.
Dendritic cells can then migrate and reach the site where newborn T cells reside. Herein, Dendritic cells communicate with T cells (fig. 1C). The expression of cancer cell extracts at the cell surface by Dendritic cells is crucial to ensure the activation of T cells. Once Dendritic cell - T cell contact occurs, T cells are able to ensure effective antitumour responses against the cancer cells that express mentioned molecules on their surface (fig. 1D) with the subsequent killing of those cancer cells (fig 1E). These events represent the basis of anticancer immunity.

How can cancer cells escape from the immune system's attacks?
Unsurprisingly, cancer cells have developed several strategies to escape from the immune system’s attacks. Mechanisms of those are still often unknown and are addressed by researchers all over the globe. Cancer cells can affect the function of Dendritic cells by inhibiting their migration to the tumour site or by interfering with the capture process. This might explain the failure of immunotherapy in some cases. As mentioned above, the mechanism through which part of cancer cells are internalized and digested by Dendritic cells is a complex multi-step process that is still not completely understood. In the cancer context, this process could be hampered at every step, preventing the activation of T cells. Cancer cells can also hide from the immune system surveillance and escape T cell recognition by reducing the expression of cell surface molecules. As explained before, the expression of tumour markers is fundamental for the killing activity of T cells.

A quick look into the future
Overall, these are only a few examples to explain the different strategies, still under investigation, used by cancer cells to avoid antitumour immune responses. Current immunotherapy approaches aim to overcome the immune resistance of cancer cells by restoring and/or boosting the antitumour activity of immune surveillance. Although immunotherapy has highlighted promising results so far, further studies are required to elucidate all the mechanisms underlying anticancer immunity and escape strategies developed by cancer cells. This will help the scientific community to improve current immunotherapy concepts and to design novel approaches to defeat cancer.

Alice Senni (ESR7)