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Peer-reviewedCC BYResearch and Practice in Thrombosis and Haemostasis

Distinct changes in plasma protein profiles of cancer patients receiving immune checkpoint inhibitors versus chemotherapy: implications for thrombosis risk and adverse outcomes

  • Eleonora Camilleri1
  • Nikola Vladic2
  • Cornelia Englisch2
  • Daniel Steiner2
  • Matthias Preusser3
  • Anna S. Berghoff3
  • Thorsten Fuereder3
  • Julia M. Berger3
  • L. Renee Ruhaak4
  • Suzanne C. Cannegieter5
  • Bart J.M. van Vlijmen6
  • Frederikus A. Klok7
1 more authors
  • Cihan Ay2
7 affiliations
  1. 1Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands
  2. 2Division of Hematology and Hemostaseology, Department of Medicine I, Medical University of Vienna, Vienna, Austria
  3. 3Division of Oncology, Department of Medicine I, Medical University of Vienna, Vienna, Austria; Christian Doppler Laboratory for Personalized Immunotherapy, Department of Medicine I, Medical University of Vienna, Vienna, Austria
  4. 4Department of Clinical Chemistry and Laboratory Medicine, Leiden University Medical Center, Leiden, The Netherlands
  5. 5Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands; Division of Thrombosis and Hemostasis, Department of Medicine, Leiden University Medical Center, Leiden, The Netherlands; Einthoven Laboratory for Vascular and Regenerative Medicine, Leiden University Medical Center, Leiden, The Netherlands
  6. 6Division of Thrombosis and Hemostasis, Department of Medicine, Leiden University Medical Center, Leiden, The Netherlands; Einthoven Laboratory for Vascular and Regenerative Medicine, Leiden University Medical Center, Leiden, The Netherlands
  7. 7Division of Thrombosis and Hemostasis, Department of Medicine, Leiden University Medical Center, Leiden, The Netherlands
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Abstract

Background: Chemotherapy and immune checkpoint inhibitors (ICIs) are distinct anticancer treatments. We studied their impact on plasma protein profiles in cancer patients, potentially providing insight into treatment-specific prothrombotic mechanisms. Objectives: To compare baseline and longitudinal changes in protein profiles of patients with non–small cell lung cancer or head and neck cancer receiving ICI or chemotherapy. Methods: We analyzed a matched cohort of 30 treatment-naïve patients from the Vienna Cancer and Thrombosis and Bleeding (CAT-BLED) study (10 non–small cell lung cancer and 5 head and neck cancer pairs). Plasma was collected before treatment, after 3 weeks, and at 3 months. We used quantitative protein mass spectrometry to measure 159 protein levels. Longitudinal changes were evaluated using linear mixed models with multiple testing correction. Results: Baseline protein profiles clustered by treatment assignment. Patients starting ICIs showed higher immune-related protein levels (eg, CD5 antigen-like, immunoglobulin mu chain C) and lower coagulation protein levels (factor[F]X, prothrombin) than those initiating chemotherapy. Two proteins changed during ICI, while 34 proteins (21%)changed during chemotherapy, with none and 12 (7%) remaining after multiple testing correction, respectively. At 3 months, chemotherapy was associated with increased levels of activated factor XIII (FXIIIa) (mean difference: 0.30; 95% confidence interval [CI], 0.06-0.54) and B (0.18; 95% CI, 0.03-0.34), fibulin-1 (0.25; 95% CI, 0.10-0.43), metalloproteinase inhibitor 2 (0.16; 95% CI, 0.02-0.31), and sex hormone-binding globulin (0.71; 95% CI, 0.23-1.14) and decreased serotransferrin (−0.10; 95% CI, −0.18 to −0.01) and cartilage acid protein 1 (−0.21; 95% CI, −0.33 to −0.09). Conclusion: In this pilot, chemotherapy and ICI were associated with treatment-specific changes in protein profiles, suggesting distinct pathophysiological processes driving thrombosis and adverse outcomes during treatment.

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Cite

BibTeXRIS
BibTeX
@article{camilleri2026distinct,
  title = {{Distinct changes in plasma protein profiles of cancer patients receiving immune checkpoint inhibitors versus chemotherapy: implications for thrombosis risk and adverse outcomes}},
  author = {Eleonora Camilleri and Nikola Vladic and Cornelia Englisch and Daniel Steiner and Matthias Preusser and Anna S. Berghoff and Thorsten Fuereder and Julia M. Berger and L. Renee Ruhaak and Suzanne C. Cannegieter and Bart J.M. van Vlijmen and Frederikus A. Klok and Cihan Ay},
  journal = {Research and Practice in Thrombosis and Haemostasis},
  year = {2026},
  month = aug,
  doi = {10.1016/j.rpth.2026.106929},
  url = {https://doi.org/10.1016/j.rpth.2026.106929},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Distinct changes in plasma protein profiles of cancer patients receiving immune checkpoint inhibitors versus chemotherapy: implications for thrombosis risk and adverse outcomes
AU  - Eleonora Camilleri
AU  - Nikola Vladic
AU  - Cornelia Englisch
AU  - Daniel Steiner
AU  - Matthias Preusser
AU  - Anna S. Berghoff
AU  - Thorsten Fuereder
AU  - Julia M. Berger
AU  - L. Renee Ruhaak
AU  - Suzanne C. Cannegieter
AU  - Bart J.M. van Vlijmen
AU  - Frederikus A. Klok
AU  - Cihan Ay
PY  - 2026
DA  - 2026/08/01
JO  - Research and Practice in Thrombosis and Haemostasis
DO  - 10.1016/j.rpth.2026.106929
UR  - https://doi.org/10.1016/j.rpth.2026.106929
AB  - Background: Chemotherapy and immune checkpoint inhibitors (ICIs) are distinct anticancer treatments. We studied their impact on plasma protein profiles in cancer patients, potentially providing insight into treatment-specific prothrombotic mechanisms. Objectives: To compare baseline and longitudinal changes in protein profiles of patients with non–small cell lung cancer or head and neck cancer receiving ICI or chemotherapy. Methods: We analyzed a matched cohort of 30 treatment-naïve patients from the Vienna Cancer and Thrombosis and Bleeding (CAT-BLED) study (10 non–small cell lung cancer and 5 head and neck cancer pairs). Plasma was collected before treatment, after 3 weeks, and at 3 months. We used quantitative protein mass spectrometry to measure 159 protein levels. Longitudinal changes were evaluated using linear mixed models with multiple testing correction. Results: Baseline protein profiles clustered by treatment assignment. Patients starting ICIs showed higher immune-related protein levels (eg, CD5 antigen-like, immunoglobulin mu chain C) and lower coagulation protein levels (factor[F]X, prothrombin) than those initiating chemotherapy. Two proteins changed during ICI, while 34 proteins (21%)changed during chemotherapy, with none and 12 (7%) remaining after multiple testing correction, respectively. At 3 months, chemotherapy was associated with increased levels of activated factor XIII (FXIIIa) (mean difference: 0.30; 95% confidence interval [CI], 0.06-0.54) and B (0.18; 95% CI, 0.03-0.34), fibulin-1 (0.25; 95% CI, 0.10-0.43), metalloproteinase inhibitor 2 (0.16; 95% CI, 0.02-0.31), and sex hormone-binding globulin (0.71; 95% CI, 0.23-1.14) and decreased serotransferrin (−0.10; 95% CI, −0.18 to −0.01) and cartilage acid protein 1 (−0.21; 95% CI, −0.33 to −0.09). Conclusion: In this pilot, chemotherapy and ICI were associated with treatment-specific changes in protein profiles, suggesting distinct pathophysiological processes driving thrombosis and adverse outcomes during treatment.
SN  - 2475-0379
ER  -