PB1936 EXPRESSION LEVELS OF PD‐1 ON T CELLS IN CHRONIC MYELOID LEUKEMIA
Authors: Lee M.Y. , Park C.‐J. , Cho Y.‐U. , Jang S. 
Published: June 2019

Background:There are several ways for malignant cells to increase their number. One of them is to use immune checkpoints protecting malignant cells from immune‐mediated injury. Upregulation of immune checkpoints contributes immune escape and tumor growth. Tyrosine kinase inhibitors (TKI) have improved the outcome of chronic myeloid leukemia (CML). TKI is generally known to inhibit the target BCR‐ABL1 kinase in leukemic cells. However, constantly growing evidence suggests that some TKIs activate the immune system to exert the direct cytotoxic effects.Aims:In this study, we evaluated the differences in expression percentages and mean fluorescence intensity (MFI) of PD‐1 on CD4+ and CD8+ T cells in CML. We analyzed the relation between the quantitative levels of BCR‐ABL and PD‐1 expression percentages.Methods:We obtained 82 bone marrow (BM) samples from patients diagnosed as CML at Asan medical center in Korea between May 2016 and May 2017. The samples included 22 at diagnosis (20 in chronic phase; CP and 2 in blast phase; BP) and 60 at follow‐up (52 in complete hematologic remission; CHR, 1 in CP, 1 in accelerated phase; AP, and 6 in BP). All patients at follow‐up were treated with Imatinib, Dasatinib, Nilotinib and/or Radotinib. Normal BM samples were collected from 23 individuals with no evidence of hematologic malignancies as the controls. Expression of PD‐1 on T cells was measured using flow cytometric analysis.Results:The median expression level of PD‐1 on CD8+ T cells for the patients in CHR was 21.25%, which was significantly lower than those in controls, in CP and in BP (Fig. 1). At diagnosis of CML, the median expression level of PD‐1 on CD8+ T cells was 32.2%. In CML patients treated with Imatinib, the expression levels of PD‐1 on CD8+ T cells were lower than at diagnosis (respectively, P = 0.004). CML patients treated with dasatinib had lower expression of PD‐1 on CD8+ T cells compared with those at diagnosis, although statistical significance was not reached. In the nilotinib‐treated patients, there was no difference of expression levels of PD‐1 compared with those at diagnosis. The level of PD‐1 expression positively correlated with the quantitative levels of BCR/ABL detected by RT‐PCR in BM (P = 0.024, rho = 0.280). When 2 individual CML patients assessed serially, the change of disease stage and the percentage of PD‐1 expression on CD8+ T cells were related longitudinally. PD‐1 expression percentages seemed to reflect the progression of the diseases, based on very limited data.Summary/Conclusion:In conclusion, low expression of PD‐1 on CD8+ T cells plays a role in maintaining CHR in CML. And immune monitoring through the measurement of PD‐1 expression on CD8+ T cells may predict the disease course. The immunomodulatory effect appears to be different depending on the type of TKIs. Some TKIs (imatinib, dasatinib) had the effect of lowering the expression of PD‐1 on CD8+ T cells and nilotinib does not. In the case of refractory disease or resistance of imatinib or dasatinib, the use of immune checkpoints inhibitors may be helpful. In the future, it would be of interest to use immune checkpoint inhibitors with nilotinib, which seems to have less effect on downregulation of PD‐1 expression on CD8+ T cells.image