Peripheral blood proteome biomarkers distinguish immunosuppressive features of cancer progression

Immune status critically affects cancer progression and therapy responses. This study aimed to identify plasma proteome changes in immunosuppressive cancer and potential biomarkers predicting systemic immunosuppression. Mouse models of syngeneic breast tumors (benign 67NR and malignant 4T1) were used to collect plasma samples. Plasma samples from naive mice and both early- and late-stage tumor-bearing mice were subjected to liquid chromatography-mass spectrometry (LC-MS) analysis. 4T1-bearing mice showed systemic immunosuppression characterized by significant generation of myeloid-derived suppressor cells (MDSCs) as early as 7 days after tumor implantation, unlike 67NR tumors. LC-MS identified 1086 proteins across the five experimental groups, with 27 proteins showing group-specific expression in 4T1 blood compared with 67NR blood. Immune-related proteins osteopontin, lactotransferrin, calreticulin, and peroxiredoxin 2 were selected as potential biomarkers of MDSC-producing breast cancer. These markers were expressed in cancer cells or MDSC in the 4T1 model, and osteopontin and peroxiredoxin 2 were associated with low survival probability and high recurrence in patients with triple-negative breast cancer. Our findings suggest that MDSC-producing immunosuppressive cancers have unique plasma proteomes, offering additional insights into cancer immune status.