CHARACTERIZATION OF NEW MEMORY CD8+ T CELL SUBSETS FOR FUTURE IMMUNOTHERAPEUTIC INTERVENTIONS

CD8+ T cells represent the most proficient defense against malignant processes and infections. To date, the most successful long-term antitumor therapeutic strategies rely on immunotherapy. However, in order to make immunotherapy accessible to every cancer patient and to guarantee its successfulness to a broader number of patients, it is mandatory to fill the gaps in the knowledge of the mechanisms of CD8+ T cell differentiation and plastic properties. This study indeed aims at unraveling and establishing an in vitro protocol for the assessment of the features and functions of six distinct human CD8+ T cell subsets. In fact, its higher purpose is to investigate CD8+ T cell subsets in order to identify the most promising target for immunotherapeutic approaches. Among CD8+ T cell subsets, TEM1 meets most of the requirements to be considered an ideal immunotherapeutic target. Following activation in the presence of viral epitopes, TEM1 undergoes better activation, proliferation, expresses the stemness marker TCF1 and shows a high plasticity rate with conversion into TCM1 and TN-like subsets. TEM1 was found to be the most enriched subset in tumor lesions of colorectal cancer (CRC) patients characterized by microsatellite stability (MSS), a condition which is usually incompatible with immunotherapy eligibility. In the tumor microenvironment of MSS-CRC patients, TEM1 also acquires an exhausted phenotype, but a fraction was found as CXCR5+PD-1+ in both peripheral blood and tumors, thus confirming that this subset could represent a promising target in hostile tumor microenvironments