Tumor-derived lactic acid generates a unique macrophage phenotype.

Tumor microenvironment is often characterized with high lactic acid concentration and lactic acid is known to have immunomodulatory effects. In this study, we aim to study the effect of lactic acid on tumor-associated macrophages (TAMs). The TAM phenotype was evaluated in terms of invasion into soli...

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Main Author: Suhartono, Timotius Marvin.
Other Authors: School of Biological Sciences
Format: Final Year Project (FYP)
Language:English
Published: 2010
Subjects:
Online Access:http://hdl.handle.net/10356/40103
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author Suhartono, Timotius Marvin.
author2 School of Biological Sciences
author_facet School of Biological Sciences
Suhartono, Timotius Marvin.
author_sort Suhartono, Timotius Marvin.
collection NTU
description Tumor microenvironment is often characterized with high lactic acid concentration and lactic acid is known to have immunomodulatory effects. In this study, we aim to study the effect of lactic acid on tumor-associated macrophages (TAMs). The TAM phenotype was evaluated in terms of invasion into solid tumor, surface antigen expression, and cytokine secretion profile. To closely mimic the in vivo tumor microenvironment, 3D tumor spheroid model was used, in which monocytes were co-cultured with tumor cells in presence or absence of oxamate, an inhibitor of lactic acid production. We found that lactic acid inhibited monocyte infiltration into tumor spheroid and increased the expression of surface molecules involved in antigen presentation, T cell co-stimulation, and phagocytosis―functions important for antitumor immune response. In addition, lactic acid increased the secretion of pro-inflammatory factors, like IL-6, CXCL10, and G-CSF. These results suggest that lactic acid might promote a pro-inflammatory TAM phenotype with an antitumor potential.
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spelling ntu-10356/401032023-02-28T18:06:21Z Tumor-derived lactic acid generates a unique macrophage phenotype. Suhartono, Timotius Marvin. School of Biological Sciences A*STAR Singapore Immunology Network Wong Siew Cheng DRNTU::Science::Biological sciences::Microbiology Tumor microenvironment is often characterized with high lactic acid concentration and lactic acid is known to have immunomodulatory effects. In this study, we aim to study the effect of lactic acid on tumor-associated macrophages (TAMs). The TAM phenotype was evaluated in terms of invasion into solid tumor, surface antigen expression, and cytokine secretion profile. To closely mimic the in vivo tumor microenvironment, 3D tumor spheroid model was used, in which monocytes were co-cultured with tumor cells in presence or absence of oxamate, an inhibitor of lactic acid production. We found that lactic acid inhibited monocyte infiltration into tumor spheroid and increased the expression of surface molecules involved in antigen presentation, T cell co-stimulation, and phagocytosis―functions important for antitumor immune response. In addition, lactic acid increased the secretion of pro-inflammatory factors, like IL-6, CXCL10, and G-CSF. These results suggest that lactic acid might promote a pro-inflammatory TAM phenotype with an antitumor potential. Bachelor of Science in Biological Sciences 2010-06-10T05:13:03Z 2010-06-10T05:13:03Z 2010 2010 Final Year Project (FYP) http://hdl.handle.net/10356/40103 en Nanyang Technological University 38 p. application/pdf
spellingShingle DRNTU::Science::Biological sciences::Microbiology
Suhartono, Timotius Marvin.
Tumor-derived lactic acid generates a unique macrophage phenotype.
title Tumor-derived lactic acid generates a unique macrophage phenotype.
title_full Tumor-derived lactic acid generates a unique macrophage phenotype.
title_fullStr Tumor-derived lactic acid generates a unique macrophage phenotype.
title_full_unstemmed Tumor-derived lactic acid generates a unique macrophage phenotype.
title_short Tumor-derived lactic acid generates a unique macrophage phenotype.
title_sort tumor derived lactic acid generates a unique macrophage phenotype
topic DRNTU::Science::Biological sciences::Microbiology
url http://hdl.handle.net/10356/40103
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