What are the characteristics of T cells that are reactivated by immunotherapy in therapies for lung cancer? Why does immunotherapy only awaken certain types of immune system cells that are narcotized by the tumor? These questions are answered, for the first time, by a study whose results are published in The Journal of Experimental Medicine. The work is the result of collaboration between the Laboratory of Translational Immunology of Humanitas, of which Dr. Enrico Lugli is the principal investigator, and the section of robotic thoracic surgery of Humanitas led by Dr. Giulia Veronesi.
The 30-parameter flow cytometer used in Humanitas
The first authors of the study, supported by a large part of Airc, are the immunologist Jolanda Brummelman and the bioinformatics specialist Emilia Mazza. “In the study, we examined 53 patients with non-small cell lung cancer (NSCLC), at an operable stage and then underwent surgery. Using a particularly innovative technology, 30-parameter flow cytometer – we were able to define the immune properties of T cells expressing the PD-1 checkpoint with remarkable precision,” explains Dr. Lugli.
Cytometry, which in Humanitas is used with the most advanced technologies, allows individual cells to be counted, separated and recognized on the basis of specific markers. The analysis of several parameters, physical, phenotypic and functional, can take place simultaneously for tens of thousands of cells per second. Cytometry is also widely used for a more precise diagnosis of certain diseases, such as tumors. The particular cytofluorimeter present in Humanitas allows basic and translational research at very high levels, analyzing 30 parameters of each cell.
“We have demonstrated – continues Dr. Lugli – that these cells are not all the same, but are organized in a hierarchy: the youngest, identified by the membrane receptor CXCR5, remain functional and are potentially able to exert a powerful anti-tumor activity, while the most differentiated (the oldest) lose this ability. The hypothesis, therefore, is that with immunotherapy young cells in particular are awakened.
For the future, the challenge is to identify the molecular signals underlying the generation and maintenance of these cells, so as to use this information to generate armed T cells in the laboratory that can improve the response to tumors.
Immunotherapy in lung cancer
Immunotherapy with antibodies that block immune checkpoints, such as anti-PD-1/PD-L1, has recently revolutionized the clinic of several types of cancer, including some types of lung cancer, allowing patients to increase their survival. So-called checkpoints are natural brakes on our immune system. Immunotherapy acts by removing these brakes and awakens particular immune cells, the T lymphocytes, which within the tumor act narcotized by the disease.