Publication Date

5-2022

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Abstract

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.

Disciplines

Oncology

Notes

Presented at the American Society of Pediatric Hematology/Oncology (ASPHO) Annual Meeting; Pittsburgh, PA; May 4-7, 2022

Memory T Cell Populations in Human Leukemia

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