Lysophosphatidic acid inhibits CD8 T cell activation and control of tumor progression

Shannon K. Oda, Pamela Strauch, Yuko Fujiwara, Amin Al-Shami, Tamas Oravecz, Gabor Tigyi, Roberta Pelanda, Raul M. Torres

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

CD8 T lymphocytes are able to eliminate nascent tumor cells through a process referred to as immune surveillance. However, multiple inhibitory mechanisms within the tumor microenvironment have been described that impede tumor rejection by CD8 T cells, including increased signaling by inhibitory receptors. Lysophosphatidic acid (LPA) is a bioactive lysophospholipid that has been shown repeatedly to promote diverse cellular processes benefiting tumorigenesis. Accordingly, the increased expression of LPA and LPA receptors is a common feature of diverse tumor cell lineages and can result in elevated systemic LPA levels. LPA is recognized by at least 6 distinct G-protein-coupled receptors and several of which are expressed by T cells, although the precise role of LPA signaling in CD8 T cell activation and function has not been defined. Here, we demonstrate that LPA signaling via the LPA5 receptor expressed by CD8 T cells suppresses antigen receptor signaling, cell activation and proliferation in vitro and in vivo. Importantly, in a mouse melanoma model tumor-specific CD8 T cells that are LPA5-deficient are able to control tumor growth significantly better than wild-type tumor-specific CD8 T cells. Together, these data suggest that the production of LPA by tumors serves not only in an autocrine manner to promote tumorigenesis but also as a mechanism to suppress adaptive immunity and highlights a potential novel target for cancer treatment.

Original languageEnglish (US)
Pages (from-to)245-255
Number of pages11
JournalCancer immunology research
Volume1
Issue number4
DOIs
StatePublished - Oct 1 2013

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T-Lymphocytes
Neoplasms
Carcinogenesis
Lysophosphatidic Acid Receptors
Lysophospholipids
Tumor Microenvironment
lysophosphatidic acid
Adaptive Immunity
Cell Lineage
G-Protein-Coupled Receptors
T-Cell Antigen Receptor
Melanoma
Cell Proliferation
Growth

All Science Journal Classification (ASJC) codes

  • Immunology
  • Cancer Research

Cite this

Lysophosphatidic acid inhibits CD8 T cell activation and control of tumor progression. / Oda, Shannon K.; Strauch, Pamela; Fujiwara, Yuko; Al-Shami, Amin; Oravecz, Tamas; Tigyi, Gabor; Pelanda, Roberta; Torres, Raul M.

In: Cancer immunology research, Vol. 1, No. 4, 01.10.2013, p. 245-255.

Research output: Contribution to journalArticle

Oda, SK, Strauch, P, Fujiwara, Y, Al-Shami, A, Oravecz, T, Tigyi, G, Pelanda, R & Torres, RM 2013, 'Lysophosphatidic acid inhibits CD8 T cell activation and control of tumor progression', Cancer immunology research, vol. 1, no. 4, pp. 245-255. https://doi.org/10.1158/2326-6066.CIR-13-0043-T
Oda, Shannon K. ; Strauch, Pamela ; Fujiwara, Yuko ; Al-Shami, Amin ; Oravecz, Tamas ; Tigyi, Gabor ; Pelanda, Roberta ; Torres, Raul M. / Lysophosphatidic acid inhibits CD8 T cell activation and control of tumor progression. In: Cancer immunology research. 2013 ; Vol. 1, No. 4. pp. 245-255.
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