Semaphorin-3A is expressed by tumor cells and alters T-cell signal transduction and function

Alfonso Catalano, Paola Caprari, Simona Moretti, Monica Faronato, Luca Tamagnone, Antonio Procopio

Research output: Contribution to journalArticle

105 Citations (Scopus)

Abstract

An important aspect of tumor progression is the ability of cancer cells to escape detection and clearance by the immune system. Recent studies suggest that several tumors express soluble factors interfering with the immune response. Here, we show that semaphorin-3A (Sema-3A), a secreted member of the semaphorin family involved in axonal guidance, organogenesis, and angiogenesis, is highly expressed in several tumor cells. Conditioned media of Sema-3A-transfected COS-7 cells or human recombinant Sema-3A inhibited primary human T-cell proliferation and cytokines production under anti-CD3 plus anti-CD28 stimulating conditions. Sema-3A also inhibited the activation of nonspecific cytotoxic activity in mixed lymphocyte culture (MLC), as measured against K-562 cells. In contrast, suppression of Sema-3A in tumor cells with a small interfering RNA (siRNA) augmented T-cell activation. The inhibitory effect of Sema-3A in T cells is mediated by blockade of Ras/mitogen-activated protein kinase (MAPK) signaling pathway. The presence of Sema-3A increased the activation of the Ras family small GTPase Rap1 and introduction of the dominant-negative mutant of Rap1 (Rap1N17) blunted the immunoinhibitory effects of Sema-3A. These results suggest that Sema-3A inhibits primary T-cell activation and imply that it can contribute to the T-cell dysfunction in the tumor microenvironment.

Original languageEnglish
Pages (from-to)3321-3329
Number of pages9
JournalBlood
Volume107
Issue number8
DOIs
Publication statusPublished - Apr 15 2006

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Semaphorin-3A
Signal transduction
T-cells
Tumors
Signal Transduction
Cells
T-Lymphocytes
Neoplasms
Chemical activation
Semaphorins
Aptitude
Tumor Microenvironment
Monomeric GTP-Binding Proteins
Organogenesis
Lymphocytes
Immune system
COS Cells
Cell proliferation
Conditioned Culture Medium
Mitogen-Activated Protein Kinases

ASJC Scopus subject areas

  • Hematology

Cite this

Semaphorin-3A is expressed by tumor cells and alters T-cell signal transduction and function. / Catalano, Alfonso; Caprari, Paola; Moretti, Simona; Faronato, Monica; Tamagnone, Luca; Procopio, Antonio.

In: Blood, Vol. 107, No. 8, 15.04.2006, p. 3321-3329.

Research output: Contribution to journalArticle

Catalano, Alfonso ; Caprari, Paola ; Moretti, Simona ; Faronato, Monica ; Tamagnone, Luca ; Procopio, Antonio. / Semaphorin-3A is expressed by tumor cells and alters T-cell signal transduction and function. In: Blood. 2006 ; Vol. 107, No. 8. pp. 3321-3329.
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