Final Activity Report Summary - IRTALUNG (Evaluation of Immune Responses Against Highly Expressed Tumor Antigens in Non-Small Cell Lung Carcinoma; Prospects for Immunotherapy)
Over the last twenty years, cancer immunotherapy has been proposed as a promising alternative for treating this debilitating disease. The premise behind this approach is that the body defence mechanisms, namely the immune system, recognise molecules that are highly expressed by the tumours, called tumour antigens, and become capable of destroying them. These mechanisms are known to constantly survey and destroy malignantly transformed cells which are continuously produced within the body. When the mechanisms fail to do so, tumour cells develop. Enforcement of these physiologic mechanisms is believed to have the potential to render the body capable of destroying tumours with its own armoury. In spite of the serious efforts towards this direction, the effectiveness of this treatment modality remains disappointingly low.
This project aimed at clarifying some key points that affected the effectiveness of lung cancer immunotherapy. More specifically, one of the core cellular elements of the immune system mediating tumour cell destruction was the cytolytic T cell. Such cells, specific for certain tumour antigens, proved to exist in the circulation of cancer patients and their number increased after tumour antigen specific vaccination.
The project objective was to examine, using the most technically advanced and sensitive methods, how either quantitative or qualitative characteristics of these cytolytic T cells from patients with lung cancer could interfere with the effectiveness of cancer immunotherapy protocols. The obtained results were of utmost importance. The most important result was that, quantitatively, there was no difference between circulating anti-tumour specific T cells of patients with cancer and normal individuals. Interestingly, cytolytic T cells from both groups were equally effective in lysing tumour cells under experimental conditions.
Given that these T cells must have had encountered tumour antigens whilst inside the body of the cancer patient but not while inside the body of the normal individual it was expected that their inability to destroy the tumour had to be due to some other, yet unidentified, differences. Consequently, the extensions of these findings opened up new research lines, which could provide an insight as to whether such fine differences of cytolytic T cells could be responsible:
1. for rendering the immune system of cancer patients unable to survey tumour development; and
2. in case these differences were appropriately targeted, for the immune system to begin to attack tumour cells, not allowing cancer development.
This project aimed at clarifying some key points that affected the effectiveness of lung cancer immunotherapy. More specifically, one of the core cellular elements of the immune system mediating tumour cell destruction was the cytolytic T cell. Such cells, specific for certain tumour antigens, proved to exist in the circulation of cancer patients and their number increased after tumour antigen specific vaccination.
The project objective was to examine, using the most technically advanced and sensitive methods, how either quantitative or qualitative characteristics of these cytolytic T cells from patients with lung cancer could interfere with the effectiveness of cancer immunotherapy protocols. The obtained results were of utmost importance. The most important result was that, quantitatively, there was no difference between circulating anti-tumour specific T cells of patients with cancer and normal individuals. Interestingly, cytolytic T cells from both groups were equally effective in lysing tumour cells under experimental conditions.
Given that these T cells must have had encountered tumour antigens whilst inside the body of the cancer patient but not while inside the body of the normal individual it was expected that their inability to destroy the tumour had to be due to some other, yet unidentified, differences. Consequently, the extensions of these findings opened up new research lines, which could provide an insight as to whether such fine differences of cytolytic T cells could be responsible:
1. for rendering the immune system of cancer patients unable to survey tumour development; and
2. in case these differences were appropriately targeted, for the immune system to begin to attack tumour cells, not allowing cancer development.