Distinct changes in plasma protein profiles of cancer patients receiving immune checkpoint inhibitors versus chemotherapy: implications for thrombosis risk and adverse outcomes.
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.
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.
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.
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).
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.
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.
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.
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).
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.
Authors
Camilleri Camilleri, Vladic Vladic, Englisch Englisch, Steiner Steiner, Preusser Preusser, Berghoff Berghoff, Fuereder Fuereder, Berger Berger, Ruhaak Ruhaak, Cannegieter Cannegieter, van Vlijmen van Vlijmen, Klok Klok, Ay Ay
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