The Expression And Mechanism Of Tim3 And Pd-1 On T Cells In Patients With Multiple Myeloma

Objective: To investigate the expression and the role of Tim3 and Pd-1on T cells in patients with multiple myeloma(MM).Consistently discuss the clinical significance of Tim3 and Pd-1expression on T cells and the mechanism of Tim3-mediated immune escape.Methods: 1.Clinical data of 34 patients with MM were collected.2.The samples of peripheral blood and bone marrow were collected from these 34 patients before and after treatment.The samples of peripheral blood from 14 healthy volunteers were gathered as normal control.The samples of bone marrow from 11 nonmalignant hematological patients were also gathered as normal control.We used the methods of immune fluorescence labeling and flow cytometry to detect expression of Tim3 and Pd-1on T cells.3.Then investigated the effect of chemotherapy on the expression of Tim3 and Pd-1 on T cells in MM patients.4.Discussed the clinical significance of Tim3 and Pd-1 expression on T cells in MM patients.5.Lastly,We detected the expression of IFN-? on T cells to investigate the effect of Tim3 on T cell function in MM patients.Results: 1.Of the 34 MM patients,17 were men and 17 were women.Among them,there were 10 cases at ISS stage ?,9 cases at ISS stage II,13 cases at ISS stage III.Among the above MM patients,there were 20 patients who received two courses of chemotherapy(PAD,PDD or PTD).After two courses of chemotherapy,14 cases achieved partial remission(PR),6 cases achieved minimal remission(MR).2.1(1)The level of Tim3 expression on CD4+ T cells in peripheral blood from MM patients(2.28±1.25)% was significantly higher than that in normal controls group(1.32 ± 0.95)%(P = 0.003).The level of Pd-1 expression on CD4+ T cells in peripheral blood from MM patients(16.64±5.92)% was significantly higher than that in normal controls group(12.13 ± 5.13)%(P = 0.0093).2.1(2)The level of Tim3 expression on CD4+ T cells in bone marrow from MM patients(3.01±1.42)% was significantly higher than that in normal controls group(1.99 ± 0.60)%(P = 0.0127).The level of Pd-1 expression on CD4+ T cells in bone marrow from MM patients(18.74±4.97)% was significantly higher than that in normal controls group(13.55 ± 4.13)%(P = 0.005).2.1(3)In newly diagnosed MM patients,The levels of Tim3 and Pd-1 expression on CD4+ T cells in bone marrow were higher than those in peripheral blood,the difference was statistically significant(P = 0.0018 and 0.0003,respectively).2.2(1)The level of Tim3 expression on CD8+ T cells in peripheral blood from MM patients(7.38±3.32)% was significantly higher than that in normal controls group(2.87± 1.56)%(P < 0.0001).The level of Pd-1 expression on CD8+ T cells in peripheral blood from MM patients(20.52±7.56)% was significantly higher than that in normal controls group(12.44 ± 4.35)%(P = 0.0002).2.2(2)The level of Tim3 expression on CD8+ T cells in bone marrow from MM patients(9.09±3.49)% was significantly higher than that in normal controls group(4.65± 1.98)%(P = 0.0001).The level of Pd-1 expression on CD8+ T cells in bone marrow from MM patients(23.56±8.39)% was significantly higher than that in normal controls group(14.45 ±3.91)%(P = 0.0002).2.2(3)In newly diagnosed MM patients,The levels of Tim3 and Pd-1 expression on CD8+ T cells in bone marrow were higher than those in peripheral blood,the difference was statistically significant(P = 0.001 and 0.0004,respectively).3.(1)In MM patients who achieved partial remission after two courses of chemotherapy(PAD,PDD or PTD),The level of Tim3 expression on CD8+ T cells in peripheral blood was declined[(3.79 ± 2.06)%VS(6.79 ± 2.96)%,P=0.0082].(2)In MM patients who achieved partial remission after two courses of chemotherapy(PAD,PDD or PTD),The level of Tim3 expression on CD8+ T cells in bone marrow was declined[(5.70 ± 2.40)%VS(9.19± 3.46)%,P=0.0047].4.The level of Tim3 on bone marrow CD8+ T cells in MM patients at ISS I-II stage(7.33 ± 2.24)% was lower than that in MM patients at ISS III stage(9.95 ± 3.47)%,the difference was statistically significant(P = 0.0279).5.The IFN-? secreting level in bone marrow Tim3+CD8+T cells(2.46 ± 0.74)% was decreased than Tim3-CD8+T cells(5.35 ± 2.59)%,the difference was statistically significant(P=0.0007).The IFN-? secreting level in bone marrow Tim3+CD4+T cells(1.33 ± 0.67)% was decreased than Tim3-CD4+T cells(3.95 ± 2.38)%,the difference was statistically significant(P=0.0003).Conclusion:1.The expression levels of Tim3 and Pd-1 on CD4+ and CD8+ T cells in newly diagnosed MM patients were significantly higher than those in normal subjects,especially in bone marrow microenvironment.2.In MM patients who achieved partial remission after two courses of chemotherapy(PAD,PDD or PTD),The level of Tim3 expression on CD8+ T cells was declined.3.At the time of initial diagnosis,The level of Tim3 expression on bone marrow CD8+T cells in MM patients was significantly related with the ISS stage.4.At the time of initial diagnosis,The IFN-? secreting level in Tim3+ T cells was decreased than Tim3-T cells.This reveals that Tim3 and Pd-1 are correlated with process of MM,and the expression level of Tim3 is related to the treatment response and prognosis of MM.Tim3-mediated inhibition of T cell function is also one of the mechanisms of myeloma immune escape.Further research is expected to explore the myeloma pathogenesis and new clinical treatment.