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Background Incorporating the immune system into cancer management is an area of robust research. Treatment modalities aimed at activating cytotoxic T cells against malignancies include immune checkpoint inhibitors, bispecific T-cell engagers, and chimeric antigen receptor (CAR) tumor-specific T cells. Most anti-cancer T cell research is narrowly focused, but knowledge about the nature of diverse sub-populations of T cells in cancer, particularly memory T cells, is vital prior to potential incorporation into therapies. T memory stem cells (Tscm) are of interest due to their longevity and powerful abilities of self-renewal and creating the full spectrum of memory CD8+ T cells, including central memory (Tcm) and effector memory cells (Tem). Objective To determine potential presence and frequency of memory T cell populations in human leukemia at diagnosis and after induction chemotherapy. Design/Method Children’s Mercy Cancer Center Biorepository provided samples from 16 patients with premature B cell acute lymphoblastic leukemia (pre-B ALL) from peripheral blood (PB) and/or bone marrow (BM). Timepoints were diagnosis and day 29 (D29) of induction chemotherapy. Flow cytometric analysis of cytotoxic memory T cell populations was performed and analyzed using descriptive statistics and the t-test. Results Despite sample variability, the absolute cell counts were not significantly different. The live cell percent was lower at diagnosis than D29 (PB- 57.2% vs 79.4%, p=0.001; BM- 41.7% vs 77.0%, p<0.001). T cell frequencies were lower at D29 (PB- 14.8% vs 5.74%, p=0.014; BM- 9.5% vs 5.9%, p=0.217). CD4+ and CD8+ T cells were not significantly different between diagnosis and D29. Among CD8+ T cells, naïve cells markedly increased from diagnosis to D29 (PB- 53.6% vs 82.2%, p < 0.001; BM- 38.8% vs 80.3%, p < 0.001) with a corresponding significant decrease in Tem (PB- 15.1% vs 4.2%, p=0.002; BM- 21.6% vs 4.7%, p < 0.001). Tscm (reported as a % of CD8+ T cells) were detected in all samples at diagnosis (PB range- 0.49-12.2%; BM range- 0.12-4.4%). After induction, two patients had no Tscm detected. The remainder demonstrated varying numbers of Tscm (PB range- 0.038-23.4%; BM range- 0.013-17.4%). Differences between diagnosis and D29 were not significant; however, percentages of Tscm were lower in 9 of 12 patients after chemotherapy. Conclusion Induction chemotherapy led to decreased differentiated CD8+ T cells with recovery of mostly naïve cells by D29. Furthermore, we established the presence of Tscm in most pediatric pre-B ALL samples. The decline of Tscm in most patients requires functional analyses to determine their role in leukemia and potential for use in immunotherapy.
McElroy, Sara; Tao, Fang; Szarejko, John; and Perry, John M., "Memory T Cell Populations in Human Leukemia" (2022). Posters. 272.