Succinate in the tumor microenvironment affects tumor growth and modulates tumor associated macrophages

Sahil Inamdar; Abhirami P. Suresh; Joslyn L. Mangal; Nathan D. Ng; Alison Sundem; Hoda Shokrollahzadeh Behbahani; Thomas E. Rubino; Jordan R. Yaron; Taravat Khodaei; Matthew Green; Marion Curtis; Abhinav P. Acharya

doi:10.1016/j.biomaterials.2023.122292

Succinate in the tumor microenvironment affects tumor growth and modulates tumor associated macrophages

Sahil Inamdar, Abhirami P. Suresh, Joslyn L. Mangal, Nathan D. Ng, Alison Sundem, Hoda Shokrollahzadeh Behbahani, Thomas E. Rubino, Jordan R. Yaron, Taravat Khodaei, Matthew Green, Marion Curtis, Abhinav P. Acharya

Research output: Contribution to journal › Article › peer-review

4 Scopus citations

Abstract

Succinate is an important metabolite that modulates metabolism of immune cells and cancer cells in the tumor microenvironment (TME). Herein, we report that polyethylene succinate (PES) microparticles (MPs) biomaterial mediated controlled delivery of succinate in the TME modulates macrophage responses. Administering PES MPs locally with or without a BRAF inhibitor systemically in an immune-defective aging mice with clinically relevant BRAF^V600E mutated YUMM1.1 melanoma decreased tumor volume three-fold. PES MPs in the TME also led to maintenance of M1 macrophages with up-regulation of TSLP and type 1 interferon pathway. Impressively, this led to generation of pro-inflammatory adaptive immune responses in the form of increased T helper type 1 and T helper type 17 cells in the TME. Overall, our findings from this challenging tumor model suggest that immunometabolism-modifying PES MP strategies provide an approach for developing robust cancer immunotherapies.

Original language	English (US)
Article number	122292
Journal	Biomaterials
Volume	301
DOIs	https://doi.org/10.1016/j.biomaterials.2023.122292
State	Published - Oct 2023

Keywords

Cancer
Immunometabolism
Macrophages
Melanoma
Succinate

ASJC Scopus subject areas

Biophysics
Bioengineering
Ceramics and Composites
Biomaterials
Mechanics of Materials

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10.1016/j.biomaterials.2023.122292

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title = "Succinate in the tumor microenvironment affects tumor growth and modulates tumor associated macrophages",

abstract = "Succinate is an important metabolite that modulates metabolism of immune cells and cancer cells in the tumor microenvironment (TME). Herein, we report that polyethylene succinate (PES) microparticles (MPs) biomaterial mediated controlled delivery of succinate in the TME modulates macrophage responses. Administering PES MPs locally with or without a BRAF inhibitor systemically in an immune-defective aging mice with clinically relevant BRAFV600E mutated YUMM1.1 melanoma decreased tumor volume three-fold. PES MPs in the TME also led to maintenance of M1 macrophages with up-regulation of TSLP and type 1 interferon pathway. Impressively, this led to generation of pro-inflammatory adaptive immune responses in the form of increased T helper type 1 and T helper type 17 cells in the TME. Overall, our findings from this challenging tumor model suggest that immunometabolism-modifying PES MP strategies provide an approach for developing robust cancer immunotherapies.",

keywords = "Cancer, Immunometabolism, Macrophages, Melanoma, Succinate",

author = "Sahil Inamdar and Suresh, {Abhirami P.} and Mangal, {Joslyn L.} and Ng, {Nathan D.} and Alison Sundem and Behbahani, {Hoda Shokrollahzadeh} and Rubino, {Thomas E.} and Yaron, {Jordan R.} and Taravat Khodaei and Matthew Green and Marion Curtis and Acharya, {Abhinav P.}",

note = "Publisher Copyright: {\textcopyright} 2023 Elsevier Ltd",

year = "2023",

month = oct,

doi = "10.1016/j.biomaterials.2023.122292",

language = "English (US)",

volume = "301",

journal = "Biomaterials",

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T1 - Succinate in the tumor microenvironment affects tumor growth and modulates tumor associated macrophages

AU - Inamdar, Sahil

AU - Suresh, Abhirami P.

AU - Mangal, Joslyn L.

AU - Ng, Nathan D.

AU - Sundem, Alison

AU - Behbahani, Hoda Shokrollahzadeh

AU - Rubino, Thomas E.

AU - Yaron, Jordan R.

AU - Khodaei, Taravat

AU - Green, Matthew

AU - Curtis, Marion

AU - Acharya, Abhinav P.

PY - 2023/10

Y1 - 2023/10

N2 - Succinate is an important metabolite that modulates metabolism of immune cells and cancer cells in the tumor microenvironment (TME). Herein, we report that polyethylene succinate (PES) microparticles (MPs) biomaterial mediated controlled delivery of succinate in the TME modulates macrophage responses. Administering PES MPs locally with or without a BRAF inhibitor systemically in an immune-defective aging mice with clinically relevant BRAFV600E mutated YUMM1.1 melanoma decreased tumor volume three-fold. PES MPs in the TME also led to maintenance of M1 macrophages with up-regulation of TSLP and type 1 interferon pathway. Impressively, this led to generation of pro-inflammatory adaptive immune responses in the form of increased T helper type 1 and T helper type 17 cells in the TME. Overall, our findings from this challenging tumor model suggest that immunometabolism-modifying PES MP strategies provide an approach for developing robust cancer immunotherapies.

AB - Succinate is an important metabolite that modulates metabolism of immune cells and cancer cells in the tumor microenvironment (TME). Herein, we report that polyethylene succinate (PES) microparticles (MPs) biomaterial mediated controlled delivery of succinate in the TME modulates macrophage responses. Administering PES MPs locally with or without a BRAF inhibitor systemically in an immune-defective aging mice with clinically relevant BRAFV600E mutated YUMM1.1 melanoma decreased tumor volume three-fold. PES MPs in the TME also led to maintenance of M1 macrophages with up-regulation of TSLP and type 1 interferon pathway. Impressively, this led to generation of pro-inflammatory adaptive immune responses in the form of increased T helper type 1 and T helper type 17 cells in the TME. Overall, our findings from this challenging tumor model suggest that immunometabolism-modifying PES MP strategies provide an approach for developing robust cancer immunotherapies.

KW - Cancer

KW - Immunometabolism

KW - Macrophages

KW - Melanoma

KW - Succinate

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VL - 301

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Succinate in the tumor microenvironment affects tumor growth and modulates tumor associated macrophages

Abstract

Keywords

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