Telomere Shortening in Peripheral Leukocytes Is Associated With Poor Survival in Cancer Patients Treated With Immune Checkpoint Inhibitor Therapy
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Telomere Shortening in Peripheral Leukocytes Is Associated With Poor Survival in Cancer Patients Treated With Immune Checkpoint Inhibitor Therapy. / Rolles, Benjamin; Gorgulho, Joao; Tometten, Mareike; Roderburg, Christoph; Vieri, Margherita; Abels, Anne; Vucur, Mihael; Heymann, Felix; Tacke, Frank; Brümmendorf, Tim H; Luedde, Tom; Beier, Fabian; Loosen, Sven H.
In: FRONT ONCOL, Vol. 11, 19.08.2021, p. 729207.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Telomere Shortening in Peripheral Leukocytes Is Associated With Poor Survival in Cancer Patients Treated With Immune Checkpoint Inhibitor Therapy
AU - Rolles, Benjamin
AU - Gorgulho, Joao
AU - Tometten, Mareike
AU - Roderburg, Christoph
AU - Vieri, Margherita
AU - Abels, Anne
AU - Vucur, Mihael
AU - Heymann, Felix
AU - Tacke, Frank
AU - Brümmendorf, Tim H
AU - Luedde, Tom
AU - Beier, Fabian
AU - Loosen, Sven H
N1 - Copyright © 2021 Rolles, Gorgulho, Tometten, Roderburg, Vieri, Abels, Vucur, Heymann, Tacke, Brümmendorf, Luedde, Beier and Loosen.
PY - 2021/8/19
Y1 - 2021/8/19
N2 - Background: Immune checkpoint inhibitor (ICI) therapy represents a new standard of care for an increasing number of malignancies. Nevertheless, response rates and outcome of ICI treatment vary between individuals and the identification of predictive markers or hints towards immune cell exhaustion during therapy has remained a major challenge. Leukocyte telomere length is an established predictive biomarker of replicative aging and cellular proliferative potential in various hematological diseases. However, its relevance in the context of ICI therapy has not been investigated to date. Here, we analyze the age-adapted delta telomere length (ΔTL) of peripheral leukocytes as a potential predictive and prognostic marker in patients undergoing ICI therapy.Methods: Age-adapted delta telomere length (ΔTL) of 84 patients treated with ICIs for solid malignancies was measured via quantitative real-time PCR. ΔTL was correlated with outcome and clinical data.Results: ΔTL was not significantly altered between patients with different tumor entities or tumor stages and did not predict tumor response to ICI therapy. However, ΔTLs at initiation of treatment were a prognostic marker for overall survival (OS). When using a calculated ideal cut-off value, the median OS in patients with shorter ΔTL was 5.7 months compared to 18.0 months in patients showing longer ΔTL. The prognostic role of age-adapted ΔTL was further confirmed by uni- and multivariate Cox-regression analyses.Conclusion: In the present study, we demonstrate that shorter telomere lengths in peripheral blood leukocytes are associated with a significantly impaired outcome in patients receiving ICI therapy across different malignancies. We explain our findings by hypothesizing an older replicative age in peripheral leukocytes of patients with an impaired overall survival, reflected by a premature TL shortening. Whether this association is ICI-specific remains unknown. Further follow-up studies are needed to provide insights about the exact mechanism of how shortened telomeres eventually affect OS and could help guiding therapeutic decisions in future.
AB - Background: Immune checkpoint inhibitor (ICI) therapy represents a new standard of care for an increasing number of malignancies. Nevertheless, response rates and outcome of ICI treatment vary between individuals and the identification of predictive markers or hints towards immune cell exhaustion during therapy has remained a major challenge. Leukocyte telomere length is an established predictive biomarker of replicative aging and cellular proliferative potential in various hematological diseases. However, its relevance in the context of ICI therapy has not been investigated to date. Here, we analyze the age-adapted delta telomere length (ΔTL) of peripheral leukocytes as a potential predictive and prognostic marker in patients undergoing ICI therapy.Methods: Age-adapted delta telomere length (ΔTL) of 84 patients treated with ICIs for solid malignancies was measured via quantitative real-time PCR. ΔTL was correlated with outcome and clinical data.Results: ΔTL was not significantly altered between patients with different tumor entities or tumor stages and did not predict tumor response to ICI therapy. However, ΔTLs at initiation of treatment were a prognostic marker for overall survival (OS). When using a calculated ideal cut-off value, the median OS in patients with shorter ΔTL was 5.7 months compared to 18.0 months in patients showing longer ΔTL. The prognostic role of age-adapted ΔTL was further confirmed by uni- and multivariate Cox-regression analyses.Conclusion: In the present study, we demonstrate that shorter telomere lengths in peripheral blood leukocytes are associated with a significantly impaired outcome in patients receiving ICI therapy across different malignancies. We explain our findings by hypothesizing an older replicative age in peripheral leukocytes of patients with an impaired overall survival, reflected by a premature TL shortening. Whether this association is ICI-specific remains unknown. Further follow-up studies are needed to provide insights about the exact mechanism of how shortened telomeres eventually affect OS and could help guiding therapeutic decisions in future.
U2 - 10.3389/fonc.2021.729207
DO - 10.3389/fonc.2021.729207
M3 - SCORING: Journal article
C2 - 34490122
VL - 11
SP - 729207
JO - FRONT ONCOL
JF - FRONT ONCOL
SN - 2234-943X
ER -