# Peripheral blood proteome biomarkers distinguish immunosuppressive features of cancer progression

## TL;DR

This study identifies blood proteins that distinguish immunosuppressive features in cancer progression using mouse models of breast tumors.

## Contribution

The study discovers plasma proteome biomarkers linked to systemic immunosuppression in malignant breast cancer.

## Key findings

- 4T1 tumors induce systemic immunosuppression and MDSC generation earlier than 67NR tumors.
- Four immune-related proteins (osteopontin, lactotransferrin, calreticulin, and peroxiredoxin 2) are potential biomarkers for MDSC-producing breast cancer.
- Osteopontin and peroxiredoxin 2 correlate with poor survival and high recurrence in triple-negative breast cancer patients.

## Abstract

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.

Immune status significantly influences cancer progression. This study used plasma proteomics to analyze benign 67NR and malignant 4T1 breast tumor models at early and late tumor stages. Immune‐related proteins–osteopontin (Spp1), lactotransferrin (Ltf), calreticulin (Calr) and peroxiredoxin 2 (Prdx2)–were associated with systemic myeloid‐derived suppressor cell (MDSC) burden, highlighting their potential roles in malignant tumors.