One of the key hurdles lies in the immunosuppressive tumor microenvironment, where the T cell receptor experiences long-term exposure to tumor antigens, leading to T cell exhaustion. This state impedes the T cells' capacity to efficiently target and eliminate cancer cells. Identifying key regulatory...
(12)BLIMP1 and NR4A3 transcription factors reciprocally regulate antitumor CAR T cell stemness and exhaustionScience translational medicineNovember 9, 2022Jung IY, Narayan V, McDonald S, Rech AJ, Bartoszek R, Hong G, Davis MM, Xu J, Boesteanu AC, Barber-Rotenberg JS,et al.Granzyme...
Spi-1 Proto-Oncogene (SPI1) fusion genes are recurrently found in T-cell acute lymphoblastic leukemia (T-ALL) cases but are insufficient to drive leukemogenesis. Here we show that SPI1 fusions in combination with activating NRAS mutations drive an immatu
CD8+ T Cell Exhaustion in Cancer 2021, Frontiers in Immunology Show abstract T cells in health and disease 2023, Signal Transduction and Targeted Therapy BLIMP1 and NR4A3 transcription factors reciprocally regulate antitumor CAR T cell stemness and exhaustion 2022, Science Translational Medicine CD8+ ...
AML patients have an immunosuppressive microenvironment and have hallmarks of immune exhaustion: increased frequencies of regulatory T cells (Tregs)1 and myeloid-derived suppressor cells (MDSCs),2 decreased T-cell proliferation,3 elevated expression of immune checkpoint molecules4 and increased TEx vs. ...
IL-7R pathway expression by tumor-specific T-cell clonotype is significantly correlated with ICI response, higher stemness & proliferative signature,lower exhaustion and apoptosis markers, providing a strong rationale of co-targeting IL-7 to PD-1 to sustain durable tumor-specific T-cells response. ...