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

Franziska Brauneck, Leticia Oliveira-Ferrer, Jana Muschhammer, Tabea Sturmheit, Christin Ackermann, Friedrich Haag, Julian Schulze zur Wiesch, Yi Ding, Minyue Qi, Louisa Hell, Barbara Schmalfeldt, Carsten Bokemeyer, Walter Fiedler, Jasmin Wellbrock

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Introduction: Tumor-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). Methods: Phenotype 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. Results: Expression 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. Conclusion: Combined blockade of TIGIT and CD47 represents a promising approach to enhance anti-CD47-facilitated phagocytosis.

Original languageEnglish
Article number1250258
JournalFrontiers in Immunology
Volume14
DOIs
StatePublished - 2023
Externally publishedYes

Keywords

  • CD47
  • High-grade serous ovarian cancer (HGSOC)
  • TIGIT
  • phagocytosis
  • repolarization
  • tumor-associated macrophages (TAMs)

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