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Circulating and tumor-infiltrating myeloid-derived suppressor cells in cervical carcinoma patients

Liangliang Wu¹, Hongyu Liu², Hongchuan Guo³

¹Department of Oncology, Chinese PLA General Hospital, Beijing 100853, P.R. China.

Oncology Letters

|May 31, 2018

Insights

Myeloid-derived suppressor cells (MDSCs) are elevated in cervical cancer patients, suppressing T-cell activity and correlating with disease stage and metastasis. Targeting these immunosuppressive cells may enhance antitumor immunity and improve treatment efficacy.

Area of Science:

Immunology
Oncology
Cancer Research

Background:

Myeloid-derived suppressor cells (MDSCs) play a crucial immunosuppressive role in human tumors.
Specific MDSC subsets, Lin-/low HLA-DR- CD11b+CD33+, are linked to tumor staging, progression, and patient prognosis.

Purpose of the Study:

To quantify MDSCs in cervical cancer patients and healthy controls.
To investigate the association of MDSCs with clinical staging, tumor infiltration, and patient outcomes.
To characterize the immunophenotype and functional suppressive capacity of MDSCs in cervical cancer.

Main Methods:

Multiparametric flow cytometry was used to analyze peripheral blood and tumor-infiltrating MDSCs.
Phenotypic characterization of MDSCs was performed using various cell surface markers.
Co-culture experiments assessed the impact of MDSCs on T-cell proliferation and cytokine production.

Main Results:

MDSC levels were significantly higher in cervical cancer patients compared to healthy controls and correlated with clinical stage.
MDSCs were more abundant in tumor tissue than adjacent tissue and associated with relapse-free survival.
MDSCs from patients suppressed CD4+ and CD8+ T-cell proliferation and inhibited IL-2 and IFN-γ production.

Conclusions:

MDSCs exert significant immunosuppression in cervical cancer, impacting T-cell responses.
Elevated MDSCs in peripheral blood and tumors are linked to cervical cancer staging, metastasis, and relapse.
Targeting MDSCs presents a potential therapeutic strategy to boost antitumor immunity in cervical cancer.

Read full analysis

Abstract:

Myeloid-derived suppressor cells (MDSCs) serve an immunosuppressive role in human tumors. Human Lin^-/low human leukocyte antigen-antigen D related (HLA-DR^-) cluster of differentiation (CD)-11b⁺CD33⁺ MDSCs are closely linked with tumor staging, progression, clinical therapeutic efficacy and prognosis for various types of tumors. The present study employed multiparametric flow cytometry to measure the proportion of Lin^-/lowHLA-DR^-CD11b⁺CD33⁺ MDSCs in the peripheral blood of 105 cervical cancer patients and 50 healthy subjects. The level of MDSC was higher in tumor patients than in the normal control group and this was closely associated with clinical staging. Further analysis of tumor-infiltrating MDSCs was performed in 22 patients. The MDSC proportions in tumor tissue were significantly higher than those in the corresponding adjacent tissue. The phenotypic characteristics of Lin^-/lowHLA-DR^-CD11b⁺CD33⁺ MDSCs were then evaluated and the results revealed that they express high CD13 and CD39, and low CD115, CD117, CD124 and programmed cell death ligand 1; they were also devoid of CD14, CD15 and CD66b. MDSCs and T-cells from peripheral blood were sorted by flow cytometry for co-culture experiments. Lin^-/lowHLA-DR^-CD11b⁺CD33⁺ MDSCs from patients significantly inhibited the proliferation of CD4 and CD8 T-cells. Furthermore, functional analysis verified that MDSCs from cervical cancer patients could inhibit interleukin-2 and interferon-γ production from T-cells. In addition, the associations between peripheral circulating MDSCs and tumor infiltrating MDSCs, and tumor relapse and metastasis were analyzed. The number of peripheral MDSCs and MDSCs in tumor tissue were observed to be associated with relapse-free survival. Thus, MDSCs in the peripheral blood and tumors of cervical cancer patients have a significant immunosuppressive effect, and are associated with cervical cancer staging and metastasis. These results suggest that targeting MDSCs may increase antitumor immunity and increase the efficacy of cervical cancer therapies.

Keywords:

T cells cervical cancer immunosuppressive myeloid-derived suppressor cells

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