Human splenic myeloid derived suppressor cells: Phenotypic and clustering analysis

Area of Science:

• Immunology
• Oncology

Background:

• Myeloid-derived suppressor cells (MDSCs) are crucial immune suppressors implicated in various diseases, including cancer.
• MDSC frequencies in cancer patients often correlate with disease stage, grade, and patient survival.
• Previous research primarily focused on peripheral blood (PB) MDSCs, with limited investigation into splenic MDSCs.

Purpose of the Study:

• To compare the frequency, subtypes, and functionality of splenic versus peripheral blood (PB) MDSCs in gastrointestinal cancer patients.
• To identify novel MDSC subsets using comprehensive marker analysis and clustering techniques.

Main Methods:

• MDSCs were rigorously subsetted from both spleen and PB of cancer patients using a panel of markers including LIN (CD3, CD19, CD56), HLA-DR, CD11b, CD14, CD15, CD33, CD34, CD45, and CD16.
• Expression levels of T-cell suppressive enzymes (ARG1, i-NOS) and activation markers (LOX-1, PD-L1, PD-1) were analyzed.
• Clustering analysis was employed to identify distinct MDSC subsets.

Main Results:

• A significantly higher frequency of polymorphonuclear (PMN)-MDSCs and monocytic (M)-MDSCs was observed in the PB compared to the spleen of cancer patients.
• All MDSC subsets from both spleen and PB of cancer patients exhibited higher expression of ARG1 and i-NOS compared to MDSCs from healthy donors.
• Activation markers LOX-1, PD-L1, and PD-1 showed similar expression patterns across MDSC subsets in cancer patients' spleen and PB.
• Clustering analysis revealed novel subsets within PMN-, M-, and immature (i)-MDSCs.

Conclusions:

• This study provides a comprehensive comparison of splenic and PB MDSCs in gastrointestinal cancer patients, highlighting differences in frequency and functional markers.
• The findings underscore the potential role of splenic MDSCs in cancer immunity and suggest novel MDSC subsets that warrant further investigation.
• Understanding MDSC heterogeneity in different anatomical sites is critical for developing targeted immunotherapies.