Tu157 - Characterization of the Epichaperome in T Cells from Healthy Donors and Heme-malignancies Patients

Mayumi Sugita – Weill Cornell Medicine; Leandro Martinez – Weill Cornell Medicine; Gail Roboz – Weill Cornell Medicine; Richard Furman – Weill Cornell Medicine; Jeremie Martinet – Rouen University Hospital; Olivier Boyer – Rouen University Hospital; Monica Guzman – Weill Cornell Medicine

Abstract Text: The epichaperome was defined as an integrated network of proteins in cancer cells which supports tumor-associated microenvironment and cancer cell survival. Previously, we reported the biochemical tools used to measure epichaperome abundance along with the correlation between epichaperome abundance and sensitivity to epichaperome inhibitor, PU-H71. PU-H71 inhibitor showed promise in single-patient trial (Sugita et al. 2021, NPJ Precis Oncol). The patient progressed to acute myeloid leukemia (AML) after failing allo-transplant, the patient harbored a novel PML-SYK fusion. After PU-H71 treatment, the patient achieved and sustained complete remission for over 5 years. We found changes in immune cells. This led to the hypothesis of epichaperome having a role in modulating immune response, also suggesting a function in healthy immune cells. Thus, we evaluated the epichaperome levels in T cells in patients with leukemia (AML or CLL) and healthy donors. At the baseline healthy T cells exhibit epichaperome levels with an average value of 1.7 (epichaperome probe over control). Epichaperome levels were consistent across CD4+ and CD8+ subpopulations of healthy T cells. In contrast, the epichaperome levels of T cells in a malignant state appeared to be aberrant. Our results showed significantly higher levels of epichaperome in T cells in patients with leukemia when compared with healthy individuals.