The combined action of monocytic myeloid‐derived suppressor cells and mucosal‐associated invariant T cells promotes the progression of cervical cancer

Abstract

One of the most common promoters of the initiation and growth of the tumor is an immune disturbance. Numerous immune cells and inflammatory factors play a role in the tumor‐immune microenvironment. However, few studies have investigated the correlation between these immunological events and clinical consequences in cervical cancer. We measured the levels of numerous inflammatory mediators and frequencies of regulatory T cells (Tregs), myeloid‐derived suppressor cells (MDSCs) and mucosal‐associated invariant T (MAIT) cells in peripheral blood (PB) of cervical cancer patients. Cervical cancer patients showed elevated production of interleukin (IL)‐18 and plasma C‐C chemokine ligand (CCL) 3/5. Meanwhile, an accumulation of C‐C chemokine receptor 5 (CCR5) monocytic (Mo)‐MDSCs and Tregs was observed. The cervical cancer group displayed increased frequencies of CD8+, CD4+ and highly activated CD38+CD8+MAIT cells, and reduction of double‐negative (DN) and PD1(CD279+) DN MAIT cells. Importantly, it was demonstrated that MAIT cells were positively related to Mo‐MDSCs. Furthermore, an elevated concentration of PD1(CD279+) DN MAIT cells was significantly related to increased progression‐free survival of patients with cervical cancer. In conclusion, our study suggests that the combined action of Mo‐MDSCs and MAIT cells might be associated with the progression of cervical cancer, and the frequency of DN MAIT cells in the peripheral blood mononuclear cells was associated with the survival benefit of patients.

Multi-Omics Data Analyses Construct a Six Immune-Related Genes Prognostic Model for Cervical Cancer in Tumor Microenvironment

“…Multiple studies have investigated the underlying mechanisms of CC, particularly with regard to the TME, therapeutic targets, and prognostic factors ( Che et al, 2020 ; Lu et al, 2020 ; Zhao et al, 2020 ). However, the current understanding remains unsatisfactory and insufficient.…”

MAIT Cells: Partners or Enemies in Cancer Immunotherapy?

“…In addition to more total MAIT cells, the latter study also found increased CD8+ MAIT cells, CD4+ MAIT cells, and highly activated CD38+CD8+ MAIT cells in CC patients [27] (Figure 1, Table 1). Additionally, a positive correlation was found between total MAIT cells and myeloid-derived suppressor cells (MDSCs) [27], a class of cells that have been shown to suppress cytotoxic abilities [83] and proliferation of T cells [84], positively correlate with tumor burden [84], promote disease progression [83], and decrease the overall survival of melanoma patients [83]. It has been hypothesized that MAIT cells, via secretion of IL-17 and/or other pro-inflammatory cytokines, could attract MDSCs and cause accumulation in the tumor site [85].…”

“…It is evident that results vary depending on which subset of MAIT cell is analyzed. In the studies discussed below, only five evaluated the frequency and/or function of the CD4+ MAIT subset [9,12,20,21,27] (Table 1). Studies that only report the activity of CD8+ MAIT cells may be overlooking this important subset that could enhance our understanding of MAIT cell biology in cancer patients.…”

“…There is conflicting evidence regarding cervical cancer (CC), as some report decreased MAIT cells in the blood [13] and others report increased MAIT cells in the blood of CC patients [27] compared to healthy individuals (Table 1). In addition to more total MAIT cells, the latter study also found increased CD8+ MAIT cells, CD4+ MAIT cells, and highly activated CD38+CD8+ MAIT cells in CC patients [27] (Figure 1, Table 1).…”

“…There is conflicting evidence regarding cervical cancer (CC), as some report decreased MAIT cells in the blood [13] and others report increased MAIT cells in the blood of CC patients [27] compared to healthy individuals (Table 1). In addition to more total MAIT cells, the latter study also found increased CD8+ MAIT cells, CD4+ MAIT cells, and highly activated CD38+CD8+ MAIT cells in CC patients [27] (Figure 1, Table 1). Additionally, a positive correlation was found between total MAIT cells and myeloid-derived suppressor cells (MDSCs) [27], a class of cells that have been shown to suppress cytotoxic abilities [83] and proliferation of T cells [84], positively correlate with tumor burden [84], promote disease progression [83], and decrease the overall survival of melanoma patients [83].…”