Abstract
CD39 is an ectoenzyme, present on different immune cell subsets, which mediates immunosuppressive functions catalyzing ATP degradation. It is not known whether CD39 is expressed and implicated in the activity of CD8+ regulatory T lymphocytes (Treg). In this study, CD39 expression and function was analyzed in both CD8+ and CD4+CD25hi Treg from the peripheral blood of healthy donors as well as from tumor specimens. CD39 was found expressed by both CD8+ (from the majority of healthy donors and tumor patients) and CD4+CD25 hi Treg, and CD39 expression correlated with suppression activity mediated by CD8+ Treg. Importantly, CD39 counteraction remarkably inhibited the suppression activity of CD8+ Treg (both from peripheral blood and tumor microenvironment) suggesting that CD39-mediated inhibition constitutes a prevalent hallmark of their function. Collectively, these findings, unveiling a new mechanism of action for CD8+ Treg, provide new knowledge on intratumoral molecular pathways related to tumor immune escape, which could be exploited in the future for designing new biological tools for anticancer immune intervention.
| Original language | English |
|---|---|
| Pages (from-to) | 851-862 |
| Number of pages | 12 |
| Journal | Cancer Immunology, Immunotherapy |
| Volume | 62 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - May 2013 |
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Keywords
- CD39
- CD8+ Treg
- Tolerance
- Tumor immune escape
ASJC Scopus subject areas
- Cancer Research
- Oncology
- Immunology
- Immunology and Allergy
Cite this
CD39 is highly involved in mediating the suppression activity of tumor-infiltrating CD8+ T regulatory lymphocytes. / Parodi, Alessia; Battaglia, Florinda; Kalli, Francesca; Ferrera, Francesca; Conteduca, Giuseppina; Tardito, Samuele; Stringara, Silvia; Ivaldi, Federico; Negrini, Simone; Borgonovo, Giacomo; Simonato, Alchiede; Traverso, Paolo; Carmignani, Giorgio; Fenoglio, Daniela; Filaci, Gilberto.
In: Cancer Immunology, Immunotherapy, Vol. 62, No. 5, 05.2013, p. 851-862.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - CD39 is highly involved in mediating the suppression activity of tumor-infiltrating CD8+ T regulatory lymphocytes
AU - Parodi, Alessia
AU - Battaglia, Florinda
AU - Kalli, Francesca
AU - Ferrera, Francesca
AU - Conteduca, Giuseppina
AU - Tardito, Samuele
AU - Stringara, Silvia
AU - Ivaldi, Federico
AU - Negrini, Simone
AU - Borgonovo, Giacomo
AU - Simonato, Alchiede
AU - Traverso, Paolo
AU - Carmignani, Giorgio
AU - Fenoglio, Daniela
AU - Filaci, Gilberto
PY - 2013/5
Y1 - 2013/5
N2 - CD39 is an ectoenzyme, present on different immune cell subsets, which mediates immunosuppressive functions catalyzing ATP degradation. It is not known whether CD39 is expressed and implicated in the activity of CD8+ regulatory T lymphocytes (Treg). In this study, CD39 expression and function was analyzed in both CD8+ and CD4+CD25hi Treg from the peripheral blood of healthy donors as well as from tumor specimens. CD39 was found expressed by both CD8+ (from the majority of healthy donors and tumor patients) and CD4+CD25 hi Treg, and CD39 expression correlated with suppression activity mediated by CD8+ Treg. Importantly, CD39 counteraction remarkably inhibited the suppression activity of CD8+ Treg (both from peripheral blood and tumor microenvironment) suggesting that CD39-mediated inhibition constitutes a prevalent hallmark of their function. Collectively, these findings, unveiling a new mechanism of action for CD8+ Treg, provide new knowledge on intratumoral molecular pathways related to tumor immune escape, which could be exploited in the future for designing new biological tools for anticancer immune intervention.
AB - CD39 is an ectoenzyme, present on different immune cell subsets, which mediates immunosuppressive functions catalyzing ATP degradation. It is not known whether CD39 is expressed and implicated in the activity of CD8+ regulatory T lymphocytes (Treg). In this study, CD39 expression and function was analyzed in both CD8+ and CD4+CD25hi Treg from the peripheral blood of healthy donors as well as from tumor specimens. CD39 was found expressed by both CD8+ (from the majority of healthy donors and tumor patients) and CD4+CD25 hi Treg, and CD39 expression correlated with suppression activity mediated by CD8+ Treg. Importantly, CD39 counteraction remarkably inhibited the suppression activity of CD8+ Treg (both from peripheral blood and tumor microenvironment) suggesting that CD39-mediated inhibition constitutes a prevalent hallmark of their function. Collectively, these findings, unveiling a new mechanism of action for CD8+ Treg, provide new knowledge on intratumoral molecular pathways related to tumor immune escape, which could be exploited in the future for designing new biological tools for anticancer immune intervention.
KW - CD39
KW - CD8+ Treg
KW - Tolerance
KW - Tumor immune escape
UR - http://www.scopus.com/inward/record.url?scp=84877822651&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84877822651&partnerID=8YFLogxK
U2 - 10.1007/s00262-013-1392-z
DO - 10.1007/s00262-013-1392-z
M3 - Article
C2 - 23359087
AN - SCOPUS:84877822651
VL - 62
SP - 851
EP - 862
JO - Cancer Immunology and Immunotherapy
JF - Cancer Immunology and Immunotherapy
SN - 0340-7004
IS - 5
ER -