The Impact of T cell Immunity on Chemotherapy Response in Childhood Acute Lymphoblastic Leukemia
Menée à l'aide d'un modèle murin et d'échantillons sanguins prélevés sur 102 enfants atteints d'une leucémie lymphoblastique aiguë, cette étude analyse les effets des lymphocytes T sur la réponse des cellules cancéreuses à une chimiothérapie
Although acute lymphoblastic leukemia (ALL) is highly responsive to chemotherapy, it is unknown how and which host immune factors influence the long-term remission of this cancer. To this end, we systematically evaluated the effects of T cell immunity on Ph+ ALL therapy outcomes. Using a murine Arf-/-BCR-ABL1 B-ALL model, we showed that loss of T cells in the host drastically increased leukemia relapse following dasatinib or cytotoxic chemotherapy. Although ABL1 mutations emerged early during dasatinib treatment in both immunocompetent and immunocompromised hosts, T cell immunity was essential for suppressing the outgrowth of drug-resistant leukemia. Bulk and single-cell transcriptome profiling of T cells during therapy pointed to the activation Type I immunity-related cytokine signaling linked to long-term leukemia remission in mice. Consistent with these observations, IFNG and IL12 directly modulated dasatinib anti-leukemia efficacy in vivo. Finally, we evaluated peripheral blood immune cell composition in 102 children with ALL during chemotherapy and observed a significant association of T cell abundance with treatment outcomes. Together, these results suggest that T cell immunity plays pivotal roles in maintaining long-term remission of ALL, highlighting that the interplay between host immunity and drug resistance can be harnessed to improve ALL chemotherapy outcomes.
Blood , résumé, 2021