Heterogeneity and prognostic influence of tumor-infiltrating gamma-delta T lymphocytes in colon cancer patients
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1
Dipartimento di Biotecnologie Mediche e Forensi- Università di Palermo, Italy
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2
Università degli Studi di Palermo, Dipartimento di Discipline Chirurgiche ed Oncologiche, Italy
Tumors grow in a complex and intricated network of epithelial and mesenchymal cells, inflammatory and immune cells and the characterization of immune contexture is a major prognostic factor for patients survival and represent a target for innovative cancer therapies.
We characterized colon cancer-infiltrating gamma-delta T cells in a cohort of 70 patients in terms of phenotype and effector functions and and correlated the immunological analysis with clinicophatological features of colon cancer. Results show that Vdelta1 T cells were the predominant population in the vast majority of specimens and upon short term mitogen in vitro stimulation produced IL-10, while Vgamma9Vdelta2 T cells were found uniformly at lower proportion in most of the patients, had a predominant terminally-differentiated effector memory (TEMRA) CD45RA+CD27- phenotype, expressed cytotoxic molecules as perforin and granzyme B and upon short term in vitro stimulation with phosphoantigen produced pro-inflammatory cytokines as IL-17 and IFNgamma in different combinations.
Correlation with different clinicopathologic features demonstrates that higher percentage of tumor-infiltrating Vgamma9Vdelta2 T cells are found in well differentiated tumors and in patients with early-stage disease and absence of metastasis, moreover, intratumoral gamma-delta T cell numbers are positively correlated with overall survival of colon cancer patients.
In conclusion, our results highlight the role of gamma-delta T cells against colorectal cancer cells and suggest that immune response mediated by gamma-delta T lymphocytes may contribute to the immunosurveillance of colon cancer. These finding may foster the development of novel alternative or adjuvant therapies targeting gamma-delta T cells for the treatment of colon cancer patients.
Keywords:
gamma-delta T cells,
Colon Cancer,
immunosurveillance,
Immunotherapy,
tumor immunity
Conference:
15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013.
Presentation Type:
Abstract
Topic:
Innate immunity
Citation:
Lo Presti
E,
Meraviglia
S,
Cicero
G,
Orlando
V,
Buccheri
S,
La Manna
M,
Di Liberto
D,
Cutrera
S,
Caccamo
N,
Dieli
F and
Dieli
F
(2013). Heterogeneity and prognostic influence of tumor-infiltrating gamma-delta T lymphocytes in colon cancer patients.
Front. Immunol.
Conference Abstract:
15th International Congress of Immunology (ICI).
doi: 10.3389/conf.fimmu.2013.02.00956
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Received:
27 Jun 2013;
Published Online:
22 Aug 2013.
*
Correspondence:
Dr. Elena Lo Presti, Dipartimento di Biotecnologie Mediche e Forensi- Università di Palermo, Palermo, Italy, elena.lopresti@cnr.it