Evaluation of immune checkpoints and tissue residency markers on NK cells from colorectal cancer patients

CRC is known to be the third most common cancer diagnosed wordwide. A mixture of genetic and epigenetic modifications contributes to CRC etiology. Currently, surgery represents the principal treatment for complete removal of the tumor. However, many cases of CRC are diagnosed at an advanced stage and, despite surgery, develop recurrences or disseminations that can even end in death. For this reason it is very important to identify new biomarkers in the early stages of tumor progression. In these three years of PhD, I’ve focused my studies on the analysis of NK cells in PB, tumor and tumor-free mucosa samples derived from CRC patients at different tumor stages with the aim of highlighting the presence of possible phenotypic variations and of their correlation to the compartment of origin or disease stage. It has been evaluated with particular attention the expression of different inhibitory immune-checkpoint receptors such as KIRs, NKG2A, PD-1, TIM-3, TIGIT, and of other markers, such as NKG2C and CD57, which can allow the identification of particular NK cell subsets. An additional goal of this study has been to identify the presence of tissue-resident NK cells (trNK) by specific marker (CD103 and CD49a) and phenotypically characterize them to verify differences with the circulating NK cells. In fact, verifying the presence of trNK cells in these pathologic tissues and understanding which receptors they express could pave the way for more specific therapies to enhance the antitumor NK cell function in situ. In conclusion, these analyses would be important to better understand why NK cells display a reduced anti-tumoral activity and to propose new innovative immunotherapic approaches for CRC patients.