The results of a new study suggest an important role for T-cell immunity in treatment outcomes in the setting of acute lymphoblastic leukemia (ALL). Findings of this study were reported in the journal Blood.
“In this study, we investigated the role of T-cell immunity in chemotherapy outcomes in ALL,” the study investigators explained in their report.
In performing the study, the researchers used murine Arf–/– BCR-AB1L B-cell ALL cells injected into both immunocompetent and immunocompromised mice. Mice were later treated with dasatinib, dexamethasone, and mercaptopurine (6-MP). The researchers analyzed characteristics related to cell populations related to T-cell immunity and leukemia-related outcomes in these mice.
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The researchers found that with dasatinib treatment, immunocompetent mice showed better survival than immunocompromised mice did that were depleted in T-cell immunity. The survival difference was even greater when mice were treated with a combination of dasatinib and dexamethasone. Efficacy with 6-MP also appeared better in the immunocompetent mice. Further analyses showed that CD4 and CD8 T cells both appeared important for the antileukemic efficacy of dasatinib in mice of this study.
The T315I mutation in the BCR-ABL1 protein had previously been associated with resistance to dasatinib in Arf–/– BCR-AB1L B-cell ALL. In this study, most immunocompetent mice that relapsed lacked mutations in this protein and had their relapses after dasatinib withdrawal, and with relapses that remained dasatinib sensitive. However, most immunocompromised mice that relapsed had developed the T315I mutation and experienced relapse while still receiving dasatinib treatment, with dasatinib resistance confirmed in vitro.
Further study of transcriptomic patterns in T-cell subpopulations suggested key roles for interferon-gamma and interleukin-12 (IL-12) in immune surveillance of ALL. Additionally, mice treated with dasatinib experienced a significantly longer survival when additionally treated with IL-12.
The researchers applied their findings from analyses in mice to prediction of outcomes in a cohort of 102 children with ALL, based on immune cell composition. In patients considered to have low T-cell levels, the event-free survival rate was 76.83%, compared with 100% in patients considered to have high T-cell levels (P =.024). In an adjusted analysis, T-cell levels maintained prognostic value (P =.0083).
Additionally, in these patients, relapse-free survival rates were 79.75% with low T-cell levels and 100% with high T-cell levels (P =.034). Further analysis suggested a higher ratio of T cells to monocytes seemed to be associated with better rates for both event-free (P =.031) and relapse-free (P =.047) survival.
“In summary, our findings provide novel insights into the mechanisms by which host factors influence the success of ALL therapy and point to potential therapeutic strategies to further improve the cure rate in this aggressive cancer,” the study investigators concluded in their report.
Reference
Li Y, Yang X, Sun Y, et al. Impact of T-cell immunity on chemotherapy response in childhood acute lymphoblastic leukemia. Blood. 2022;140(13):1507-1521. doi:10.1182/blood.2021014495
