Identifying dysfunctional T-cell signatures in patients with aggressive diffuse large B cell lymphoma (DLBCL).

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Therapies that "reawaken" and redirect the immune system have shown huge promise in patients with advanced malignancy. "Reawakening" the immune system can be achieved using bispecific antibodies (BsAbs). These bind to tumour cells on one arm and to normal T cells on the other, thereby creating an immune synapse which facilitates tumour destruction. The BsAb glofitamab binds to the B cell specific CD20 and T-cell-specific CD3. 50% of lymphoma patients receiving glofitamab in early phase clinical trials entered a durable complete remission; glofitamab is the most potent CD20 antibody to date. Nevertheless, not all patients respond and the reasons for this are not clear. One possibility is that the T-cell functions are impaired in lymphoma patients. Surprisingly, functions of the immune system have not been extensively characterised in patients with DLBCL.The aims of this study are therefore to determine the nature and functions of T cell populations in DLBCL using a multiomic approach (multi-parameter flow cytometry, single cell proteomics and RNA Sequencing). Telomere length will be determined in collaboration with TeloNostiX. These data will be integrated with whole exome sequencing data from primary tumours and will define optimal conditions for the use of BsAbs in earlier phases of treatment.