Potential Role of Diabetes Mellitus-Associated T Cell Senescence in Epithelial Ovarian Cancer Omental Metastasis.

Rhianne Broadway,Dmitry A Zinovkin,Nikita M Patel,Yulia S Korneva,Amal El-Briri,Md Zahidul I Pranjol,Lucy E Hillier

doi:10.3390/life11080788

Abstract

Epithelial ovarian cancer (EOC) is one of the most common causes of cancer-related deaths among women and is associated with age and age-related diseases. With increasing evidence of risks associated with metabolic inflammatory conditions, such as obesity and type 2 diabetes mellitus (T2DM), it is important to understand the complex pathophysiological mechanisms underlying cancer progression and metastasis. Age-related conditions can lead to both genotypic and phenotypic immune function alterations, such as induction of senescence, which can contribute to disease progression. Immune senescence is a common phenomenon in the ageing population, which is now known to play a role in multiple diseases, often detrimentally. EOC progression and metastasis, with the highest rates in the 75–79 age group in women, have been shown to be influenced by immune cells within the “milky spots” or immune clusters of the omentum. As T2DM has been reported to cause T cell senescence in both prediabetic and diabetic patients, there is a possibility that poor prognosis in EOC patients with T2DM is partly due to the accumulation of senescent T cells in the omentum. In this review, we explore this hypothesis with recent findings, potential therapeutic approaches, and future directions.

Highlights

Epithelial ovarian cancer (EOC) is the eighth most common cause of cancer-related deaths among women globally, with a survival rate of less than 50% and an average age at diagnosis of 63 years [1,2]
Given that chronic-inflammation-induced senescence is a detrimental factor associated with poor prognosis in type 2 diabetes mellitus (T2DM) and obesity comorbidities, there is a possibility that these immune cells in the ageing peritoneum of T2DM patients contribute to creating a more proinflammatory, tumour-friendly premetastatic niche for migrating EOC cells to form secondary foci
Type 2 diabetes mellitus (T2DM), a risk factor for epithelial ovarian cancer (EOC), is a chronic metabolic and inflammatory disorder that results in immune senescence

Summary

Introduction

Epithelial ovarian cancer (EOC) is the eighth most common cause of cancer-related deaths among women globally, with a survival rate of less than 50% and an average age at diagnosis of 63 years [1,2]. Given that chronic-inflammation-induced senescence is a detrimental factor associated with poor prognosis in T2DM and obesity comorbidities, there is a possibility that these immune cells in the ageing peritoneum of T2DM patients contribute to creating a more proinflammatory, tumour-friendly premetastatic niche for migrating EOC cells to form secondary foci. The omentum recruited effector T cells and produced CD4+ and CD8+ T cell responses to peritoneal antigens, suggesting that the adaptive immune system is a key component in inflammatory conditions, such as a growing tumour [44]

Diabetes Mellitus-Associated T Cell Senescence

Age-Related Immunosenescence and Cancer

Findings

Conclusions