Immunosuppressive M2 TAMs represent a promising target population to enhance phagocytosis of ovarian cancer cells in vitro
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Immunosuppressive M2 TAMs represent a promising target population to enhance phagocytosis of ovarian cancer cells in vitro. / Brauneck, Franziska; Schmalfeldt, Barbara; Muschhammer, Jana; Sturmheit, Tabea; Ackermann, Christin; Haag, Friedrich; Schulze Zur Wiesch, Julian; Ding, Yi; Qi, Minyue; Hell, Louisa; Schmalfeldt, Barbara; Bokemeyer, Carsten; Fiedler, Walter; Wellbrock, Jasmin.
In: FRONT IMMUNOL, Vol. 14, 2023, p. 1250258.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Immunosuppressive M2 TAMs represent a promising target population to enhance phagocytosis of ovarian cancer cells in vitro
AU - Brauneck, Franziska
AU - Schmalfeldt, Barbara
AU - Muschhammer, Jana
AU - Sturmheit, Tabea
AU - Ackermann, Christin
AU - Haag, Friedrich
AU - Schulze Zur Wiesch, Julian
AU - Ding, Yi
AU - Qi, Minyue
AU - Hell, Louisa
AU - Schmalfeldt, Barbara
AU - Bokemeyer, Carsten
AU - Fiedler, Walter
AU - Wellbrock, Jasmin
N1 - Copyright © 2023 Brauneck, Oliveira-Ferrer, Muschhammer, Sturmheit, Ackermann, Haag, Schulze zur Wiesch, Ding, Qi, Hell, Schmalfeldt, Bokemeyer, Fiedler and Wellbrock.
PY - 2023
Y1 - 2023
N2 - 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.
AB - 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.
KW - Humans
KW - Female
KW - CD47 Antigen/genetics
KW - Tumor-Associated Macrophages/metabolism
KW - Phagocytosis
KW - Ovarian Neoplasms/metabolism
KW - Receptors, Immunologic/genetics
KW - Tumor Microenvironment
U2 - 10.3389/fimmu.2023.1250258
DO - 10.3389/fimmu.2023.1250258
M3 - SCORING: Journal article
C2 - 37876933
VL - 14
SP - 1250258
JO - FRONT IMMUNOL
JF - FRONT IMMUNOL
SN - 1664-3224
ER -
