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

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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. Aims To compare baseline and longitudinal changes in protein profiles of patients with non-small cell lung cancer (NSCLC) or head and neck cancer receiving ICI or chemotherapy. Methods We analyzed a matched cohort of 30 treatment-naïve patients from the Vienna CAT-BLED study (10 NSCLC and five head and neck cancer pairs). Plasma was collected before treatment, after three weeks, and three 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 proteins (e.g., CD5 antigen-like, immunoglobulin mu chain C) and lower coagulation proteins levels (factor[F]X, prothrombin) than those initiating chemotherapy. Two proteins changed during ICI, while 34(21%) proteins changed during chemotherapy, with none and 12(7%) remaining after multiple testing correction, respectively. At three months, chemotherapy was associated with increased levels of FXIIIA (mean difference: 0.30, 95%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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