Regulation of Tumor Immunity by Lysophosphatidic Acid

The tumor microenvironment (TME) may be best conceptualized as an ecosystem comprised of cancer cells interacting with a multitude of stromal components such as the extracellular matrix (ECM), blood and lymphatic networks, fibroblasts, adipocytes, and cells of the immune system. At the center of thi...

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Published inCancers Vol. 12; no. 5; p. 1202
Main Authors Lee, Sue Chin, Dacheux, Mélanie A., Norman, Derek D., Balázs, Louisa, Torres, Raul M., Augelli-Szafran, Corinne E., Tigyi, Gábor J.
Format Journal Article
LanguageEnglish
Published Switzerland MDPI AG 10.05.2020
MDPI
Subjects
Adipocytes
Angiogenesis
Antigens
Cancer
Cytokines
Cytotoxicity
Enzymes
Extracellular matrix
Fibroblasts
Granulocytes
Immune system
Immunomodulation
Investigations
Kinases
Lymphocytes
Lysophosphatidic acid
Metastases
Metastasis
Neutrophils
Ovarian cancer
Peptides
Proteins
Review
T cell receptors
Tumors
lysophosphatidic acid
LPAR5
autotaxin
immune checkpoint
immune cells
immunosuppression
tumor microenvironment
LPA
cytotoxic T cells
immunosurveillance
immunoediting
tumor-associated macrophages
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Abstract The tumor microenvironment (TME) may be best conceptualized as an ecosystem comprised of cancer cells interacting with a multitude of stromal components such as the extracellular matrix (ECM), blood and lymphatic networks, fibroblasts, adipocytes, and cells of the immune system. At the center of this crosstalk between cancer cells and their TME is the bioactive lipid lysophosphatidic acid (LPA). High levels of LPA and the enzyme generating it, termed autotaxin (ATX), are present in many cancers. It is also well documented that LPA drives tumor progression by promoting angiogenesis, proliferation, survival, invasion and metastasis. One of the hallmarks of cancer is the ability to modulate and escape immune detection and eradication. Despite the profound role of LPA in regulating immune functions and inflammation, its role in the context of tumor immunity has not received much attention until recently where emerging studies highlight that this signaling axis may be a means that cancer cells adopt to evade immune detection and eradication. The present review aims to look at the immunomodulatory actions of LPA in baseline immunity to provide a broad understanding of the subject with a special emphasis on LPA and cancer immunity, highlighting the latest progress in this area of research.
AbstractList The tumor microenvironment (TME) may be best conceptualized as an ecosystem comprised of cancer cells interacting with a multitude of stromal components such as the extracellular matrix (ECM), blood and lymphatic networks, fibroblasts, adipocytes, and cells of the immune system. At the center of this crosstalk between cancer cells and their TME is the bioactive lipid lysophosphatidic acid (LPA). High levels of LPA and the enzyme generating it, termed autotaxin (ATX), are present in many cancers. It is also well documented that LPA drives tumor progression by promoting angiogenesis, proliferation, survival, invasion and metastasis. One of the hallmarks of cancer is the ability to modulate and escape immune detection and eradication. Despite the profound role of LPA in regulating immune functions and inflammation, its role in the context of tumor immunity has not received much attention until recently where emerging studies highlight that this signaling axis may be a means that cancer cells adopt to evade immune detection and eradication. The present review aims to look at the immunomodulatory actions of LPA in baseline immunity to provide a broad understanding of the subject with a special emphasis on LPA and cancer immunity, highlighting the latest progress in this area of research.
The tumor microenvironment (TME) may be best conceptualized as an ecosystem comprised of cancer cells interacting with a multitude of stromal components such as the extracellular matrix (ECM), blood and lymphatic networks, fibroblasts, adipocytes, and cells of the immune system. At the center of this crosstalk between cancer cells and their TME is the bioactive lipid lysophosphatidic acid (LPA). High levels of LPA and the enzyme generating it, termed autotaxin (ATX), are present in many cancers. It is also well documented that LPA drives tumor progression by promoting angiogenesis, proliferation, survival, invasion and metastasis. One of the hallmarks of cancer is the ability to modulate and escape immune detection and eradication. Despite the profound role of LPA in regulating immune functions and inflammation, its role in the context of tumor immunity has not received much attention until recently where emerging studies highlight that this signaling axis may be a means that cancer cells adopt to evade immune detection and eradication. The present review aims to look at the immunomodulatory actions of LPA in baseline immunity to provide a broad understanding of the subject with a special emphasis on LPA and cancer immunity, highlighting the latest progress in this area of research.The tumor microenvironment (TME) may be best conceptualized as an ecosystem comprised of cancer cells interacting with a multitude of stromal components such as the extracellular matrix (ECM), blood and lymphatic networks, fibroblasts, adipocytes, and cells of the immune system. At the center of this crosstalk between cancer cells and their TME is the bioactive lipid lysophosphatidic acid (LPA). High levels of LPA and the enzyme generating it, termed autotaxin (ATX), are present in many cancers. It is also well documented that LPA drives tumor progression by promoting angiogenesis, proliferation, survival, invasion and metastasis. One of the hallmarks of cancer is the ability to modulate and escape immune detection and eradication. Despite the profound role of LPA in regulating immune functions and inflammation, its role in the context of tumor immunity has not received much attention until recently where emerging studies highlight that this signaling axis may be a means that cancer cells adopt to evade immune detection and eradication. The present review aims to look at the immunomodulatory actions of LPA in baseline immunity to provide a broad understanding of the subject with a special emphasis on LPA and cancer immunity, highlighting the latest progress in this area of research.
Author Norman, Derek D.
Dacheux, Mélanie A.
Balázs, Louisa
Augelli-Szafran, Corinne E.
Tigyi, Gábor J.
Torres, Raul M.
Lee, Sue Chin
AuthorAffiliation 3 Department of Immunology & Microbiology, University of Colorado School of Medicine, Denver, CO 80045, USA; raul.torres@cuanschutz.edu
1 Department of Physiology, University of Tennessee Health Science Center, Memphis, TN 38163, USA; slee84@uthsc.edu (S.C.L.); mdacheux@uthsc.edu (M.A.D.); dnorman7@uthsc.edu (D.D.N.)
4 Department of Chemistry, Drug Discovery Division, Southern Research, Birmingham, AL 35205, USA; caugelli-szafran@southernresearch.org
2 Department of Pathology and Laboratory Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, USA; cziczam@comcast.net
AuthorAffiliation_xml – name: 1 Department of Physiology, University of Tennessee Health Science Center, Memphis, TN 38163, USA; slee84@uthsc.edu (S.C.L.); mdacheux@uthsc.edu (M.A.D.); dnorman7@uthsc.edu (D.D.N.)
– name: 2 Department of Pathology and Laboratory Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, USA; cziczam@comcast.net
– name: 3 Department of Immunology & Microbiology, University of Colorado School of Medicine, Denver, CO 80045, USA; raul.torres@cuanschutz.edu
– name: 4 Department of Chemistry, Drug Discovery Division, Southern Research, Birmingham, AL 35205, USA; caugelli-szafran@southernresearch.org
Author_xml – sequence: 1
  givenname: Sue Chin
  surname: Lee
  fullname: Lee, Sue Chin
– sequence: 2
  givenname: Mélanie A.
  surname: Dacheux
  fullname: Dacheux, Mélanie A.
– sequence: 3
  givenname: Derek D.
  surname: Norman
  fullname: Norman, Derek D.
– sequence: 4
  givenname: Louisa
  surname: Balázs
  fullname: Balázs, Louisa
– sequence: 5
  givenname: Raul M.
  surname: Torres
  fullname: Torres, Raul M.
– sequence: 6
  givenname: Corinne E.
  surname: Augelli-Szafran
  fullname: Augelli-Szafran, Corinne E.
– sequence: 7
  givenname: Gábor J.
  orcidid: 0000-0001-5371-171X
  surname: Tigyi
  fullname: Tigyi, Gábor J.
BackLink https://www.ncbi.nlm.nih.gov/pubmed/32397679$$D View this record in MEDLINE/PubMed
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2020 by the authors. 2020
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Issue 5
Keywords lysophosphatidic acid
LPAR5
autotaxin
immune checkpoint
immune cells
immunosuppression
tumor microenvironment
LPA
cytotoxic T cells
immunosurveillance
immunoediting
tumor-associated macrophages
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Snippet The tumor microenvironment (TME) may be best conceptualized as an ecosystem comprised of cancer cells interacting with a multitude of stromal components such...
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SubjectTerms Adipocytes
Angiogenesis
Antigens
Cancer
Cytokines
Cytotoxicity
Enzymes
Extracellular matrix
Fibroblasts
Granulocytes
Immune system
Immunomodulation
Investigations
Kinases
Lymphocytes
Lysophosphatidic acid
Metastases
Metastasis
Neutrophils
Ovarian cancer
Peptides
Proteins
Review
T cell receptors
Tumors
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Title Regulation of Tumor Immunity by Lysophosphatidic Acid
URI https://www.ncbi.nlm.nih.gov/pubmed/32397679
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Volume 12
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