A group of researchers of IRCCS San Raffaele Hospital and Vita-Salute San Raffaele University, headed by Chiara Bonini, Full Professor of Hematology at UniSR Faculty of Medicine and Surgery, has shown how it is possible to identify, monitor over time and characterize anti-tumor T-cells in patients suffering from acute myeloid leukemia and how we could exploit inhibition mechanisms activated by tumor to evade recognition by our immune system.

Ultimate purpose of this research project is to identify new reagents that might lead to the development of therapeutic products for patients with acute myeloid leukemia. The study has been recently published on the prestigious journal Science Advances.

The research project

Thanks to the meticulous study on anti-tumor T-cells in patients’ peripheral blood after hematopoietic stem cell transplantation, researchers observed how these cells were present in 90% of the analyzed patients, but, unfortunately, we are not able to carry out their function as “killers” of the immune system. “The reason lies in the fact that these anti-tumor receptors are subject to “functional exhaustion”, which is caused by the presence on their surface of molecules that can “turn them off”, phenomenon that seems to be particularly relevant in patients with recurrence of the disease” explains Francesco Manfredi, first author of the study.

Dr. Eliana Ruggiero, co-last author of the study adds: “Through the combination of the detailed analysis of proteins expressed on anti-tumor t-cells with transcriptome and peptidome sequencing technologies – this last activity, in collaboration with Professor Vincenzo Cerullo of University of Helsinki -, we identified not only a library of TCR, i.e. proteins expressed on t-cells surface able to recognize tumor, but also molecules expressed by tumor cells that in the future might be used as new therapeutic target”.

Using “molecular scissors” through the CRISPR/Cas9 technique, which are able to “cut” and eliminate specific genes, researchers subsequently generated an “army” of tumor-specific t-cells, inserting into cells anti-tumor identified TCR.

Dr. Chiara Bonini underlines: “this study paves the way for new treatments for patients suffering from acute myeloid leukemia. Exploiting the presence of anti-tumor t-cells in the majority of patients and the inability of these cells to recognize tumor, we have worked to identifiy new reagents which could be used, in the future, to expand treatment options of patients affected by this pathology”.