The prognostic and predictive value of IKZF1 and IKZF3 expression in T-cells in patients with multiple myeloma
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The prognostic and predictive value of IKZF1 and IKZF3 expression in T-cells in patients with multiple myeloma. / Awwad, Mohamed H S; Kriegsmann, Katharina; Plaumann, Julian; Benn, Michael; Hillengass, Jens; Raab, Marc S; Bertsch, Uta; Munder, Markus; Weisel, Katja; Salwender, Hans Jürgen; Hänel, Mathias; Fenk, Roland; Dürig, Jan; Müller-Tidow, Carsten; Goldschmidt, Hartmut; Hundemer, Michael.
In: ONCOIMMUNOLOGY, Vol. 7, No. 10, 2018, p. e1486356.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - The prognostic and predictive value of IKZF1 and IKZF3 expression in T-cells in patients with multiple myeloma
AU - Awwad, Mohamed H S
AU - Kriegsmann, Katharina
AU - Plaumann, Julian
AU - Benn, Michael
AU - Hillengass, Jens
AU - Raab, Marc S
AU - Bertsch, Uta
AU - Munder, Markus
AU - Weisel, Katja
AU - Salwender, Hans Jürgen
AU - Hänel, Mathias
AU - Fenk, Roland
AU - Dürig, Jan
AU - Müller-Tidow, Carsten
AU - Goldschmidt, Hartmut
AU - Hundemer, Michael
PY - 2018
Y1 - 2018
N2 - Purpose: While recent studies described the role of IKZF1/3 proteins in multiple myeloma (MM) cells, few have highlighted the significance of IKZF1/3 expression in T-cells. In this study we examine the prognostic and predictive value of IKZF1/3 expression in T-cells in patients with MM stage III. Experimental design: We analysed the IKZF1/3 expression levels in T-cells from 45 MM stage I (MMI) and 50 newly diagnosed MM stage III (MMIII) patients, according to Durie-Salmon staging system, by flow cytometry to examine their prognostic and predictive value. We also combined in vivo observations with in vitro assays to determine the effect of IKZF1/3 expression on the T-cell immunophenotype and anti-tumour T-cell response in 162 MMIII patients. Results: We found that high IKZF3, but not IKZF1, expression in T-cells correlates with superior overall survival in MMIII patients treated with immunomodulatory drugs (thalidomide, lenalidomide and pomalidomide). Moreover, we show that higher IKZF3 expression in T-cells inhibits myeloma-specific T-cell response in vitro and that the immunophenotype of patients with high IKZF3 expression shows features that are contrary to the changes induced by immunomodulatory drugs. Although we observed higher IKZF3 expression levels in T-cells from patients with MMIII compared to MMI, IKZF3 expression was unaffected by the tumour microenvironment. Conclusion: In conclusion, IKZF3 expression in T-cells is a predictive value for clinical outcome in MMIII patients treated with immunomodulatory drugs due to its profound modulation of T-cell functionality.
AB - Purpose: While recent studies described the role of IKZF1/3 proteins in multiple myeloma (MM) cells, few have highlighted the significance of IKZF1/3 expression in T-cells. In this study we examine the prognostic and predictive value of IKZF1/3 expression in T-cells in patients with MM stage III. Experimental design: We analysed the IKZF1/3 expression levels in T-cells from 45 MM stage I (MMI) and 50 newly diagnosed MM stage III (MMIII) patients, according to Durie-Salmon staging system, by flow cytometry to examine their prognostic and predictive value. We also combined in vivo observations with in vitro assays to determine the effect of IKZF1/3 expression on the T-cell immunophenotype and anti-tumour T-cell response in 162 MMIII patients. Results: We found that high IKZF3, but not IKZF1, expression in T-cells correlates with superior overall survival in MMIII patients treated with immunomodulatory drugs (thalidomide, lenalidomide and pomalidomide). Moreover, we show that higher IKZF3 expression in T-cells inhibits myeloma-specific T-cell response in vitro and that the immunophenotype of patients with high IKZF3 expression shows features that are contrary to the changes induced by immunomodulatory drugs. Although we observed higher IKZF3 expression levels in T-cells from patients with MMIII compared to MMI, IKZF3 expression was unaffected by the tumour microenvironment. Conclusion: In conclusion, IKZF3 expression in T-cells is a predictive value for clinical outcome in MMIII patients treated with immunomodulatory drugs due to its profound modulation of T-cell functionality.
KW - Journal Article
U2 - 10.1080/2162402X.2018.1486356
DO - 10.1080/2162402X.2018.1486356
M3 - SCORING: Journal article
C2 - 30288348
VL - 7
SP - e1486356
JO - ONCOIMMUNOLOGY
JF - ONCOIMMUNOLOGY
SN - 2162-402X
IS - 10
ER -