Immunosuppressive M2 TAMs represent a promising target population to enhance phagocytosis of ovarian cancer cells in vitro

Frontiers in Immunology

Immunology

Tabea Sturmheit¹  Minyue Qi²  Barbara Schmalfeldt³  Leticia Oliveira-Ferrer³  Yi Ding³  Louisa Hell³  Julian Schulze zur Wiesch⁴  Christin Ackermann⁵  Walter Fiedler⁶  Carsten Bokemeyer⁶  Jasmin Wellbrock⁶  Jana Muschhammer⁶  Franziska Brauneck⁷  Friedrich Haag⁸ 

[1] 2cureX GmbH, Hamburg, Germany;Bioinformatics Core, University Medical Center Hamburg-Eppendorf, Hamburg, Germany;Department of Gynecology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany;Department of Infectious Diseases, University Medical Center Hamburg-Eppendorf, Hamburg, Germany;Department of Infectious Diseases, University Medical Center Hamburg-Eppendorf, Hamburg, Germany;Institute of Hematopathology Hamburg HpH, Hamburg, Germany;Department of Oncology, Hematology and Bone Marrow Transplantation with Section Pneumology, Hubertus Wald University Cancer Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany;Department of Oncology, Hematology and Bone Marrow Transplantation with Section Pneumology, Hubertus Wald University Cancer Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany;Mildred Scheel Cancer Career Center HaTriCS4, University Medical Center Hamburg-Eppendorf, Hamburg, Germany;Institute of Immunology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany;

关键词: High-grade serous ovarian cancer (HGSOC);    tumor-associated macrophages (TAMs);    TIGIT;    repolarization;    CD47;    phagocytosis;   

DOI  :  10.3389/fimmu.2023.1250258

 received in 2023-06-29, accepted in 2023-09-04,  发布年份 2023

来源: Frontiers

【 摘 要 】

IntroductionTumor-associated macrophages (TAMs) represent an important cell population within the tumor microenvironment, but little is known about the phenotype and function of these cells. The present study aims to characterize macrophages in high-grade serous ovarian cancer (HGSOC).MethodsPhenotype and expression of co-regulatory markers were assessed on TAMs derived from malignant ascites (MA) or peripheral blood (PB) by multiparametric flow cytometry. Samples were obtained from HGSOC patients (n=29) and healthy donors (HDs, n=16). Additional expression analysis was performed by RNAseq (n=192). Correlation with clinically relevant parameters was conducted and validated by a second patient cohort (n=517). Finally, the role of TIGIT in repolarization and phagocytosis was investigated in vitro.ResultsExpression of the M2-associated receptors CD163, CD204, and CD206, as well as of the co-regulatory receptors TIGIT, CD226, TIM-3, and LAG-3 was significantly more frequent on macrophages in HGSOC than in HDs. CD39 and CD73 were broadly expressed on (mainly M2) macrophages, but without a clear clustering in HGSOC. CD163 mRNA levels were higher in TAMs from patients with residual tumor mass after surgery and associated with a shorter overall survival. In addition, TIGIT expression was associated with a higher tumor grading, indicating a prognostic relevance of M2 infiltration in HGSOC. TIGIT blockade significantly reduced the frequency of M2 macrophages. Moreover, combined blockade of TIGIT and CD47 significantly increased phagocytosis of ovarian cancer cells by TAMs in comparison to a single blockade of CD47.ConclusionCombined blockade of TIGIT and CD47 represents a promising approach to enhance anti-CD47-facilitated phagocytosis.

【 授权许可】

Unknown   
Copyright © 2023 Brauneck, Oliveira-Ferrer, Muschhammer, Sturmheit, Ackermann, Haag, Schulze zur Wiesch, Ding, Qi, Hell, Schmalfeldt, Bokemeyer, Fiedler and Wellbrock