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Immune-checkpoint inhibitors: immunophenotyping and clinical outcome to predict response at Barretos Cancer Hospital


Cancer immunotherapy is based on the premise that tumors can be recognized and can be attacked by an activated immune system. However, tumor cells develop mechanisms to thwart immune recognition and response. The immune checkpoints modulate the homeostasis of co-stimulatory and co-inhibitory signals, which are critical to maintaining immune tolerance besides modulating the physiological immune responses. However, despite the high response rate to immunotherapy, some patients are refractory to therapy or acquire resistance. Therefore, the characterization of the immune tumor microenvironment that drives or prevents effective responses to therapy is fundamental for understanding and expanding the use of immunotherapy. To investigate immunological markers that may distinguish responders from non-responders to therapy with immunological checkpoint inhibitors in patients with advanced melanoma and Non-small-cell lung carcinoma (NSCLC). One hundred patients who underwent anti-PD-1/PD-L1 or anti-CTLA-4 immunotherapy will be selected. The immunophenotypic profile of the immune checkpoint inhibitors will be evaluated on peripheral blood T lymphocytes and tumor infiltrating lymphocytes (TIL) by flow cytometry. The expression profile of relevant genes to cancer immune response will be analyzed in tumor samples (paraffin and CD45 negative cells), by PanCancer IO 360 Gene Expression Panel, using the nCounter NanoString platform. The expression profile of lymphocytes (from blood and tumor), paraffin material (containing tumor + TIL) and negative CD45 cells will be correlated with demographic, clinical, histopathological data and mainly with the therapeutic response and patient survival. Essential as a platform for this and later studies will be the enhancement and implementation of in vitro T lymphocyte exhaustion model, which will be performed by sequential stimulation with CD3/CD28 dynabeads. (AU)

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