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Review
. 2021 Apr 15;22(8):4091.
doi: 10.3390/ijms22084091.

The Cancer Stem Cell Niche in Ovarian Cancer and Its Impact on Immune Surveillance

Srishti Jain  1 , Stephanie L Annett  1 , Maria P Morgan  1 , Tracy Robson  1
Affiliations
Review

The Cancer Stem Cell Niche in Ovarian Cancer and Its Impact on Immune Surveillance

Srishti Jain et al. Int J Mol Sci. .

Abstract

Ovarian cancer is an aggressive gynaecological cancer with extremely poor prognosis, due to late diagnosis as well as the development of chemoresistance after first-line therapy. Research advances have found stem-like cells present in ovarian tumours, which exist in a dynamic niche and persist through therapy. The stem cell niche interacts extensively with the immune and non-immune components of the tumour microenvironment. Significant pathways associated with the cancer stem cell niche have been identified which interfere with the immune component of the tumour microenvironment, leading to immune surveillance evasion, dysfunction and suppression. This review aims to summarise current evidence-based knowledge on the cancer stem cell niche within the ovarian cancer tumour microenvironment and its effect on immune surveillance. Furthermore, the review seeks to understand the clinical consequences of this dynamic interaction by highlighting current therapies which target these processes.

Keywords: cancer stem cells; immune surveillance; ovarian cancer; tumour microenvironment.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The estimated incidence and mortality rate for gynaecological cancers in European females of all ages, 2020. The values are expressed as age-standardised rate per 100,000 population. The mortality-to-incidence ratio (MIR) for ovarian cancer (0.64) is the highest among all gynaecological cancers and more than twice as high as that for breast cancer (0.25). Source: European Cancer Information System, European Commission.
Figure 2
Figure 2
Models of ovarian cancer tumor development and heterogenity. (A) The stochastic model—Each cell is considered biologically equivalent (clonal). Heterogeneity is attributed to genetic mutations propagated through time. All cells have tumorigenic capacity. (B) The hierarchical model—A single cell undergoes a de-differentiating mutation and forms a distinct subpopulation within the niche having stem cell-like tumorigenic potential and leading to the formation of both intermediate progenitor cells as well as terminally differentiated cells, thus contributing to heterogeneity. (C) The plasticity model—Proposes a plastic state of tumorigenic potential in the niche. Differentiated cells can be mutated to re-acquire stem cell-like properties, and the niche contains a dynamic heterogeneous population of differentiated tumour cells as well as stem cells.
Figure 3
Figure 3
Ovarian cancer stem cell (OCSC)-associated signaling pathways. OCSC signaling pathways involved in the generation and maintenance of OCSCs including the Notch pathway [10,11], Wnt signaling pathway [10,11], JAK2/STAT3 pathway [12,13,14], PI3K/PTEN/AKT pathway [15], Hippo pathway [16], NF-κB [17,18] and the Hedgehog pathway [19]. NICD—intracellular domain of Notch protein; LRP—low-density lipoprotein-related protein; JAK—Janus kinase, STAT—signal transducer and activator of transcription proteins; PI3K—phosphatidylinositol 3-kinase, PTEN—phosphatidylinositol 3,4,5—triphosphate 3-phosphatase, AKT/PKB—protein kinase B; YAP—Yes-associated protein; NF-κB—nuclear factor kappa B.
Figure 4
Figure 4
Immunosuppressive effect of the cancer stem cell niche on the tumour immune and non-immune microenvironment. Signaling molecules regulating these processes and the overall effect of the stem cell niche are outlined.
See this image and copyright information in PMC

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