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

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.