Extracellular vesicles mediated proinflammatory macrophage phenotype induced by radiotherapy in cervical cancer

Junli Ren,Guoliang Wang,Xiaodong Han,Yaqin Cui,Naiping Sun,Lili Li,Xiaoxue Zhang,Zihan Xing,Enwei Xu,Xiaoning Li,Xiaoyan Wang,Baofeng Yu

doi:10.1186/s12885-022-09194-z

Abstract

BackgroundRadiotherapy is a highly effective treatment for cervical cancer. Recent studies focused on the radiotherapy induced anti-tumor immunity. Whether tumor-derived extracellular vesicles (EVs) play roles in radiotherapy induced tumor associated macrophage (TAM) polarization remains unclear.Materials and MethodsThis study analysed the phenotype of macrophages in cancer tissue and peripheral blood of cervical cancer patients using flow cytometry analysis. The role of EVs from plasma of post-irradiated patients on M2-like transformed macrophages was assessed. The M1- and M2-like macrophages were assessed by expression of cell surface markers (CCR7, CD163) and intracellular cytokines (IL-10, TNFα and iNOS). The capacity of phagocytosis was assessed by PD-1 expression and phagocytosis of pHrodo Red E. coli bioparticles.ResultsOur results demonstrated that radiotherapy of cervical cancer induced an increase in the number of TAMs and a change in their subtype from the M2-like to the M1-like phenotype (increased expression of CCR7 and decreased expression of CD163). The EVs from plasma of post-irradiated patients facilitated the M2-like to the M1-like phenotype transition (increased expression of CCR7, TNFα and iNOS, and decreased expression of CD163 and IL-10) and increased capacity of phagocytosis (decreased PD-1 expression and increased phagocytosis of pHrodo Red E. coli bioparticles).ConclusionsOur data demonstrated that irradiation in cervical cancer patients facilitated a proinflammatory macrophage phenotype which could eventually able to mediate anti-tumor immune responses. Our findings highlight the importance of EV in the crosstalk of tumor cells and TAM upon irradiation, which potentially leading to an increased inflammatory response to cancer lesions.

Highlights

Cervical cancer, which was mainly caused by carcinogenic human papillomavirus types, continues to be a major public health problem affecting middle-aged women [1, 2]
The Extracellular vesicle (EV) from plasma of post-irradiated patients facilitated the M2-like to the M1-like phenotype transition and increased capacity of phagocytosis
Our data demonstrated that irradiation in cervical cancer patients facilitated a proinflammatory macrophage phenotype which could eventually able to mediate anti-tumor immune responses

Summary

Introduction

Cervical cancer, which was mainly caused by carcinogenic human papillomavirus types, continues to be a major public health problem affecting middle-aged women [1, 2]. Cytological screening [3, 4] and the use of vaccines against human papillomavirus [5, 6] have led to a major decline in cancer burden in several resource-rich countries, cervical cancer remains to be the most commonly diagnosed cancer and the predominant. Radiotherapy is a highly effective treatment for cervical cancer, even for patients with advanced stages [7]. Recent studies focused on the radiotherapy induced anti-tumor immunity generated by various activating and/or inhibiting factors [9, 10]. By radiotherapy induced immunogenicity cell death, the damage-associated molecular patterns from tumor cells can induce an effective anti-tumor immune response [11]. Recent studies focused on the radiotherapy induced anti-tumor immunity. Whether tumor-derived extracellular vesicles (EVs) play roles in radiotherapy induced tumor associated macrophage (TAM) polarization remains unclear

Methods

Results

Discussion

Conclusion